Non-covalent SARS-CoV-2 M^pro inhibitors developed from in silico screen hits.

ABSTRACT: M^pro, the main protease of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is essential for the viral life cycle. Accordingly, several groups have performed in silico screens to identify M^pro inhibitors that might be used to treat SARS-CoV-2 infections. We selected more than five hundred compounds from the top-ranking hits of two very large in silico screens for on-demand synthesis. We then examined whether these compounds could bind to M^pro and inhibit its protease activity. Two interesting chemotypes were identified, which were further evaluated by characterizing an additional five hundred synthesis on-demand analogues. The compounds of the first chemotype denatured M^pro and were considered not useful for further development.

SUBMITTER: Rossetti GG 

PROVIDER: S-EPMC8847420 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature