Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors.

ABSTRACT: The emergence of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an urgent public health crisis. Without available targeted therapies, treatment options remain limited for COVID-19 patients. Using medicinal chemistry and rational drug design strategies, we identify a 2-phenyl-1,2-benzoselenazol-3-one class of compounds targeting the SARS-CoV-2 main protease (M^pro). FRET-based screening against recombinant SARS-CoV-2 M^pro identified six compounds that inhibit proteolysis with nanomolar IC₅₀ values. Preincubation dilution experiments and molecular docking determined that the inhibition of SARS-CoV-2 M^pro can occur by either covalent or noncovalent mechanisms, and lead E04 was determined to inhibit M^pro

SUBMITTER: Huff S 

PROVIDER: S-EPMC8491550 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature