N-Terminal Finger Stabilizes the S1 Pocket for the Reversible Feline Drug GC376 in the SARS-CoV-2 M^pro Dimer.

ABSTRACT: The main protease (M^pro, also known as 3CL protease) of SARS-CoV-2 is a high priority drug target in the development of antivirals to combat COVID-19 infections. A feline coronavirus antiviral drug, GC376, has been shown to be effective in inhibiting the SARS-CoV-2 main protease and live virus growth. As this drug moves into clinical trials, further characterization of GC376 with the main protease of coronaviruses is required to gain insight into the drug's properties, such as reversibility and broad specificity. Reversibility is an important factor for therapeutic proteolytic inhibitors to prevent toxicity due to off-target effects. Here we demonstrate that GC376 has nanomolar K_i values with the M^pro from both SARS-CoV-2 and SARS-CoV strains. Restoring enz

SUBMITTER: Arutyunova E 

PROVIDER: S-EPMC8061786 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature