Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication.

ABSTRACT: The main protease, M^pro (or 3CL^pro) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor. Here, we show the prodrug and its parent GC373, are effective inhibitors of the M^pro from both SARS-CoV and SARS-CoV-2 with IC₅₀ values in the nanomolar range. Crystal structures of SARS-CoV-2 M^pro with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication

SUBMITTER: Vuong W 

PROVIDER: S-EPMC7453019 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature