BC-11 is a covalent TMPRSS2 fragment inhibitor that impedes SARS-CoV-2 host cell entry.

ABSTRACT: Host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated via priming of its spike glycoprotein by the human transmembrane protease serine 2 (TMPRSS2). Although camostat and nafamostat are two highly potent covalent TMPRSS2 inhibitors, they nevertheless did not hold promise in COVID-19 clinical trials, presumably due to their short plasma half-lives. Herein, we report an integrative chemogenomics approach based on computational modeling and in vitro enzymatic assays, for repurposing serine-targeted covalent inhibitors. This led to the identification of BC-11 as a covalent TMPRSS2 inhibitor displaying a unique selectivity profile for serine proteases, ascribable to its boronic acid warhead. BC-11 showed modest inhibition of SARS-CoV-2 (omicron variant) s

SUBMITTER: Moumbock AFA 

PROVIDER: S-EPMC9874818 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature