Open AccessBepridil is potent against SARS-CoV-2 in vitro
Author(s) -
Erol C. Vatansever,
Kun Yang,
Aleksandra Drelich,
Kaci C. Kratch,
Chia Chuan Cho,
Kempaiah Rayavara,
Jason C. Hsu,
Drake M. Mellott,
Shiqing Xu,
Chien-Te K. Tseng,
Wenshe Ray Liu
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2012201118
Subject(s) - bepridil , covid-19 , pharmacology , in vitro , docking (animal) , virology , medicine , chemistry , infectious disease (medical specialty) , biochemistry , pathology , disease , verapamil , nursing , outbreak , calcium
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% (IC 50 ) 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% (EC 50 ) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.