Bepridil is potent against SARS-CoV-2 in vitro.

Abstract

Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^p^ro). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC₅₀) value below 100 μM in inhibiting M^p^ro, and, importantly, three, that is, pimozide, ebastine, and bepridil, are basic molecules that potentiate dual functions by both raising endosomal pH to interfere with SARS-CoV-2 entry into the human cell host and inhibiting M^p^ro in infected cells. A live virus-based modified microneutralization assay revealed that bepridil possesses significant anti-SARS-CoV-2 activity in both Vero E6 and A459/ACE2 cells in a dose-dependent manner with low micromolar effective concentration, 50% (EC₅₀) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.