Related Experiment Video
Updated: Nov 17, 2025
08:41
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
3.1K
Bepridil is potent against SARS-CoV-2 in vitro
Erol C Vatansever1, Kai S Yang1, Aleksandra K Drelich2
1The Texas A&M Drug Discovery Laboratory, Department of Chemistry, Texas A&M University, College Station, TX 77843.
Summary
Bepridil, pimozide, and ebastine show potential against SARS-CoV-2 by inhibiting the main protease and blocking viral entry. Bepridil demonstrated significant antiviral activity in cell models, warranting clinical investigation for COVID-19 treatment.
Area of Science:
- Virology and Drug Discovery
- Computational Chemistry and Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant global health threat.
- Repurposing existing Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines offers a rapid therapeutic strategy.
- Targeting the SARS-CoV-2 main protease (Mpro) is a key strategy for inhibiting viral replication.
Purpose of the Study:
- To identify FDA/EMA-approved small molecules that inhibit SARS-CoV-2 Mpro.
- To evaluate the dual-function potential of identified inhibitors in blocking viral entry and replication.
- To assess the in vitro antiviral efficacy of promising drug candidates against SARS-CoV-2.
Main Methods:
- Computational docking analysis was employed to screen approximately 30 FDA/EMA-approved small molecules for Mpro inhibition.
- In vitro assays were performed to determine the half-maximal inhibitory concentration (IC50) against Mpro.
- A modified microneutralization assay using live SARS-CoV-2 was conducted to evaluate antiviral activity in cell lines (Vero E6, A549/ACE2).
Main Results:
- Six small molecules exhibited IC50 values below 100 μM for Mpro inhibition.
- Three basic molecules—pimozide, ebastine, and bepridil—demonstrated dual functions: raising endosomal pH to impede viral entry and inhibiting Mpro.
- Bepridil displayed significant dose-dependent anti-SARS-CoV-2 activity with low micromolar effective concentration, 50% (EC50) values in both cell lines.
Conclusions:
- Bepridil, pimozide, and ebastine are promising candidates for repurposing against SARS-CoV-2 due to their dual mechanisms of action.
- Bepridil exhibits potent in vitro antiviral efficacy, suggesting its potential as a therapeutic agent for COVID-19.
- Clinical trials evaluating bepridil for COVID-19 treatment are strongly recommended based on these findings.
