Challenges for Targeting SARS-CoV-2 Proteases as a Therapeutic Strategy for COVID-19.

ABSTRACT: Two proteases produced by the SARS-CoV-2 virus, the main protease and papain-like protease, are essential for viral replication and have become the focus of drug development programs for treatment of COVID-19. We screened a highly focused library of compounds containing covalent warheads designed to target cysteine proteases to identify new lead scaffolds for both M^pro and PL^pro proteases. These efforts identified a small number of hits for the M^pro protease and no viable hits for the PL^pro protease. Of the M^pro hits identified as inhibitors of the purified recombinant protease, only two compounds inhibited viral infectivity in cellular infection assays. However, we observed a substantial drop in antiviral potency upon expression of TM

SUBMITTER: Steuten K 

PROVIDER: S-EPMC7901237 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature