Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture.

Allison Bakovic,Farhang Alem,Jane A Harness,Warren K Weston,Nishank Bhalla,Aarthi Narayanan,Theresa L Chang,Kenneth Risner

doi:10.3390/v13020271

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.

Highlights

IntroductionThe global coronavirus disease-19 (COVID-19) pandemic resulting from infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the novel coronavirus, has resulted in excess of 100 million infections and 2.1 million deaths worldwide, including over 25 million cases and 425,000 fatalities in the United States [1]
Cell culture supernatants from vehicle-treated and brilacidin-treated cells were collected at 16 h postinfection, and the SARS-CoV-2 infectious titer in the supernatants was quantitated by plaque assay and compared to the DMSO-treated control
The ongoing global COVID-19 pandemic powerfully reinforces the need for therapeutic strategies that can safely and effectively address virus- and host-based events elicited during SARS-CoV-2 infection

Summary

Introduction

The global coronavirus disease-19 (COVID-19) pandemic resulting from infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the novel coronavirus, has resulted in excess of 100 million infections and 2.1 million deaths worldwide, including over 25 million cases and 425,000 fatalities in the United States [1]. 15% of COVID-19 patients will develop lung injury, including severe respiratory distress that can progress to Acute Respiratory Distress Syndrome (ARDS), often requiring prolonged ventilator support and leading to death. The prevalence of secondary bacterial infections [5,6,7,8], which can occur in up to 20% of cases among hospitalized patients, reinforces the need for a multipronged treatment approach that can address the complexities of COVID-19

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