Discovery of 2-thiobenzimidazoles as noncovalent inhibitors of SARS-CoV-2 main protease.

ABSTRACT: The discovery of antiviral agents against SARS-CoV-2 is an important step toward ending the COVID-19 pandemic and to tackle future outbreaks. In this context, the main protease (M^pro) represents an ideal target for developing coronavirus antivirals, being conserved among different strains and essential for survival. In this work, using in silico tools, we created and validated a docking protocol able to predict binders to the catalytic site of M^pro. The following structure-based virtual screening of a subset of the ZINC library (over 4.3 million unique structures), led to the identification of a hit compound having a 2-thiobenzimidazole scaffold. The inhibitory activity was confirmed using a FRET-based proteolytic assay against recombinant M^pro. Structure-a

SUBMITTER: Deodato D 

PROVIDER: S-EPMC9225965 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature