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Welcome to the CNP11-DENVRdrp-LifeChem wiki!
This repository outlines one of several projects related to our efforts to identify a small molecule that binds to the Dengue virus RNA-dependent RNA polymerase (Rdrp). This specific repository describes our efforts at identifying a new tool compound from the Life Chemicals Life Chemicals 50K Diversity 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.
This project commenced in mid-2023 with a single-point screen of 50K Life Chemicals Diversity library. Of the top-100 highest inhibiting compounds, 64 were available for purchasing. After determining the IC50 in a picogreen DENV2 assay, 5 compounds showed inhibition below 20 μM. Additional tests in an nano-luciferase DENV2 and DENV4 whole cell activity assay, showed that none of the compounds were active, possibly due to permeability issues. Testing the compounds on a gelbased DENV2 RdRp assay as well as activity on hmtRNA production showed that all compounds, except RA-2923 were active on both, indicating possible toxicity issues.
A small expansion of 12 compounds focusing on RA-2923 was purchased, but only 3 compounds showed any activity and none better than the parent compound.
This avenue was paused as a new selection from the HTS was done, generating 50 new compounds for testing.
May 2024
Update on expansion: 50 compounds were tested at single point in the nano-luciferase whole cell assay, 15 showed activity above 50% inhibition and the EC50 and whole cell toxicity are now being determined.