Easy access to α-ketoamides as SARS-CoV-2 and MERS M^pro inhibitors via the PADAM oxidation route.

ABSTRACT: SARS-CoV-2 caused worldwide the current outbreak called COVID-19. Despite multiple countermeasures implemented, there is an urgent global need for new potent and efficient antiviral drugs against this pathogen. In this context, the main protease (M^pro) of SARS-CoV-2 is an essential viral enzyme and plays a pivotal role in viral replication and transcription. Its specific cleavage of polypeptides after a glutamine residue has been considered as a key element to design novel antiviral drugs. Herein, we reported the design, synthesis and structure-activity relationships of novel α-ketoamides as covalent reversible inhibitors of M^pro, exploiting the PADAM oxidation route. The reported compounds showed μM to nM activities in enzymatic and in the antiviral cell-based assays

SUBMITTER: Pelliccia S 

PROVIDER: S-EPMC9575579 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature