Bepridil is potent against SARS-CoV-2 in vitro
Open Access
- 17 February 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (10)
- https://doi.org/10.1073/pnas.2012201118
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.Keywords
Funding Information
- Welch Foundation (A-1715)
- Texas A&M University (X Grant)
- Texas A&M University (Translational Investment Fund)
This publication has 50 references indexed in Scilit:
- Bepridil and Amiodarone Simultaneously Target the Alzheimer's Disease - and -Secretase via Distinct MechanismsJournal of Neuroscience, 2010
- AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibilityJournal of Computational Chemistry, 2009
- Interpreting Steep Dose-Response Curves in Early Inhibitor DiscoveryJournal of Medicinal Chemistry, 2006
- Engineering and characterization of a superfolder green fluorescent proteinNature Biotechnology, 2005
- Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 4. Incorporation of P1 Lactam Moieties as l-Glutamine ReplacementsJournal of Medicinal Chemistry, 1999
- BepridilDrugs, 1992
- Disposition of bepridil in laboratory animals and manXenobiotica, 1992
- Comparative efficacy of 200, 300 and 400 mg of bepridil for chronic stable angina pectorisThe American Journal of Cardiology, 1985
- Prolongation of QT interval and antiarrhythmic action of bepridilAmerican Heart Journal, 1985
- Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances.The Journal of cell biology, 1981