Structural Basis of the Main Proteases of Coronavirus Bound to Drug Candidate PF-07321332.

ABSTRACT: The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genera of coronaviruses is the substrate-binding site of the main protease (M^pro or 3CL^pro), making it an attractive target for the development of broad-spectrum drugs for multiple coronaviruses. PF-07321332, developed by Pfizer, is the first orally administered inhibitor targeting the main protease of SARS-CoV-2, which also has shown potency against other coronaviruses. Here, we report three crystal structures of the main protease of SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome (MERS)-CoV bound to the inhibitor PF-07321332. The structure

SUBMITTER: Li J 

PROVIDER: S-EPMC9044943 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature