Bepridil is potent against SARS-CoV-2 in vitro

Erol C. Vatansever, Kai S. Yang, Aleksandra K. Drelich, Kaci C. Kratch, Chia Chuan Cho, Kempaiah Rayavara Kempaiah, Jason C. Hsu, Drake M. Mellott, Shiqing Xu, Chien Te K. Tseng, Wenshe Ray Liu

Research output: Contribution to journalArticlepeer-review

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 (Mpro). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC50) value below 100 μM in inhibiting Mpro, 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 Mpro 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.

Original languageEnglish (US)
Article numbere2012201118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number10
DOIs
StatePublished - Mar 9 2021

Keywords

  • Bepridil
  • COVID-19
  • Drug repurposing
  • Main protease
  • SARS-CoV-2

ASJC Scopus subject areas

  • General

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