2. Academic Validation
  3. Bepridil is potent against SARS-CoV-2 in vitro

Bepridil is potent against SARS-CoV-2 in vitro

  • Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2012201118. doi: 10.1073/pnas.2012201118.
Erol C Vatansever 1,  Kai S Yang 1,  Aleksandra K Drelich 2,  Kaci C Kratch 1,  Chia-Chuan Cho 1,  Kempaiah Rayavara Kempaiah 2,  Jason C Hsu 2,  Drake M Mellott 3,  Shiqing Xu 1,  Chien-Te K Tseng 4 5,  Wenshe Ray Liu 6 3 7 8 9
Affiliations

Affiliations

  • 1 The Texas A&M Drug Discovery Laboratory, Department of Chemistry, Texas A&M University, College Station, TX 77843.
  • 2 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555.
  • 3 Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843.
  • 4 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555; [email protected] [email protected].
  • 5 Center of Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX 77555.
  • 6 The Texas A&M Drug Discovery Laboratory, Department of Chemistry, Texas A&M University, College Station, TX 77843; [email protected] [email protected].
  • 7 Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030.
  • 8 Department of Translational Medical Sciences, College of Medicine, Texas A&M University, Houston, TX 77030.
  • 9 Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843.
PMID: 33597253 DOI: 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

COVID-19; SARS-CoV-2; bepridil; drug repurposing; main protease.

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