Discovery of a Novel Trifluoromethyl Diazirine Inhibitor of SARS-CoV-2 M^pro.

ABSTRACT: SARS-CoV-2 M^pro is a chymotrypsin-like cysteine protease playing a relevant role during the replication and infectivity of SARS-CoV-2, the coronavirus responsible for COVID-19. The binding site of M^pro is characterized by the presence of a catalytic Cys145 which carries out the hydrolytic activity of the enzyme. As a consequence, several M^pro inhibitors have been proposed to date in order to fight the COVID-19 pandemic. In our work, we designed, synthesized and biologically evaluated MPD112, a novel inhibitor of SARS-CoV-2 M^pro bearing a trifluoromethyl diazirine moiety. MPD112 displayed in vitro inhibition activity against SARS-CoV-2 M^pro at a low micromolar level (IC₅₀ = 4.1 μM) in a FRET-based assay. Moreove

SUBMITTER: Citarella A 

PROVIDER: S-EPMC9864213 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature