Discovery of a potent covalent inhibitor that unusually distorts the catalytic dyad of SARS-CoV-2 main protease.

ABSTRACT: Proteases are versatile therapeutic targets for a wide variety of human diseases, including cancer, cardiovascular diseases, and infections by viruses, bacteria, and parasites. The main protease (M^pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has been one of the major drug targets for the treatment of COVID-19. In this study, a small-molecule covalent inhibitor, H102, of SARS-CoV-2 M^pro was developed from serial structural modifications on a compound previously reported by us to have anti-SARS-CoV-2 activity. H102 exhibited very high potency in SARS-CoV-2 M^pro inhibition with IC₅₀ of 8.8 nM and strongly prevented SARS-CoV-2 replication in VeroE6 cells

SUBMITTER: Wang J 

PROVIDER: S-EPMC12548382 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature