Combining virtual screening with cis-/trans-cleavage enzymatic assays effectively reveals broad-spectrum inhibitors that target the main proteases of SARS-CoV-2 and MERS-CoV.

ABSTRACT: The main protease (M^pro) of SARS-CoV-2 is essential for viral replication, which suggests that the M^pro is a critical target in the development of small molecules to treat COVID-19. This study used an in-silico prediction approach to investigate the complex structure of SARS-CoV-2 M^pro in compounds from the United States National Cancer Institute (NCI) database, then validate potential inhibitory compounds against the SARS-CoV-2 M^pro in cis- and trans-cleavage proteolytic assays. Virtual screening of ∼280,000 compounds from the NCI database identified 10 compounds with highest site-moiety map scores. Compound NSC89640 (coded C1) showed marked inhibitory activity against the SARS-CoV-2 M^pro in cis-/trans-cleavage assays. C1 strongly inh

SUBMITTER: Chang YJ 

PROVIDER: S-EPMC10264167 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature