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Updated: Nov 17, 2025

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture
Allison Bakovic1, Kenneth Risner1, Nishank Bhalla1
1National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.
Abstract:
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin-a de novo designed synthetic small molecule that captures the biological properties of HDPs-on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is likely to be a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 against different strains of the virus in cell culture.
Insights
Brilacidin, a synthetic small molecule, shows potent antiviral activity against SARS-CoV-2 by inhibiting viral entry and integrity. It also demonstrates synergistic effects with remdesivir, offering a potential therapeutic option for COVID-19 treatment.
Area of Science:
- Virology
- Drug Discovery
- Antimicrobial Peptides
Background:
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a global health crisis with high mortality.
- There is an urgent need for effective therapeutic interventions against SARS-CoV-2.
- Antimicrobial peptides (AMPs), or Host Defense Proteins/Peptides (HDPs), show promise in inhibiting SARS-CoV-2.
Purpose of the Study:
- To evaluate the antiviral activity of brilacidin, a synthetic HDP analog, against SARS-CoV-2.
- To investigate the mechanism of action of brilacidin against SARS-CoV-2.
- To assess the synergistic potential of brilacidin in combination with remdesivir.
Main Methods:
- Testing brilacidin's antiviral efficacy in human lung (Calu-3) and monkey (Vero) cell lines infected with SARS-CoV-2.
- Assessing the impact of brilacidin on viral entry and integrity.
- Evaluating combination therapy with remdesivir.
Main Results:
- Brilacidin demonstrated potent inhibition of SARS-CoV-2 in cell culture models.
- The mechanism involves inhibiting viral entry and disrupting viral integrity.
- Brilacidin exhibited synergistic antiviral activity when combined with remdesivir.
Conclusions:
- Brilacidin is a potent inhibitor of SARS-CoV-2 with a dual mechanism of action.
- Brilacidin shows promise as a therapeutic agent for COVID-19, particularly in combination with existing antivirals like remdesivir.
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