Hit Expansion of a Noncovalent SARS-CoV-2 Main Protease Inhibitor.

ABSTRACT: Inhibition of the SARS-CoV-2 main protease (M^pro) is a major focus of drug discovery efforts against COVID-19. Here we report a hit expansion of non-covalent inhibitors of M^pro. Starting from a recently discovered scaffold (The COVID Moonshot Consortium. Open Science Discovery of Oral Non-Covalent SARS-CoV-2 Main Protease Inhibitor Therapeutics. bioRxiv 2020.10.29.339317) represented by an isoquinoline series, we searched a database of over a billion compounds using a cheminformatics molecular fingerprinting approach. We identified and tested 48 compounds in enzyme inhibition assays, of which 21 exhibited inhibitory activity above 50% at 20 μM. Among these, four compounds with IC₅₀ values around 1 μM were found. Interestingly, despite the large search space

SUBMITTER: Glaser J 

PROVIDER: S-EPMC9003389 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature