Home
Welcome to the CNP18-DENVRdrp-VirtualScreen wiki!
This repository outlines one of several projects related to our efforts to identify a small molecular compound that binds to the Dengue virus RNA-dependent RNA polymerase (RdRp). This specific repository describes our efforts at identifying a possible hit molecule from the Enamine REAL library.
Below is a summary of the project, and the sidebar to the the right allows you to explore each step if the process further; linking to additional data, tables, and other overviews we might only reference below.
To get an overview of the READDI-AViDD project please read the Rules of Participation and Origins of the Project.
You can also explore Other Repositories related to Dengue RdRp campaign.
In mid-2023 we started a virtual screening campaign of the Enamine REAL space to help us identify new starting points for developing a probe that binds to Dengue RdRp. To guide the virtual screen, mutagenic studies supported the identification of highly conserved residues on the protein, and a previously unexplored pocket on the RdRp was identified. Using HIDDEN-GEM a preliminary library of ~1000 compounds was generated and of these 65 were send for initial testing.
This generated three hits that were used as starting point for further exploration. Initially, these showed only antiviral activity but later tests using a WaveDelta assay showed they are likely binding to RdRp. Before this data arrives a first tentative exploration for the three hits was selected from commercially available sources. These should provide information about what parts are important for binding and will guide future SAR exploration.
March 2024
- Expansion sent for testing in Pearce Lab
- Expansion sent for testing in Hirsch Lab
- Co-crystal efforts ongoing in Arnold Lab
- Testing hits on mutagenic strains in plannig to support confirmation of binding mode - Baric Lab
- Gel-based assay to confirm DENV RdRp interaction and provide information about interaction with hmtRNA - Gotte Lab