National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.
Public Health Research Institute, Rutgers, New Jersey Medical School, the State University of New Jersey, Newark, NJ 07103, USA.
Viruses. 2021 Feb 9;13(2):271. doi: 10.3390/v13020271.
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.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是一种新出现的冠状病毒病 19（COVID-19）病原体，自 2019 年首次发现以来，已在全球导致超过 200 万人死亡。全球急需治疗干预策略，可以安全地治疗 COVID-19 疾病并降低相关发病率和死亡率。越来越多的证据表明，天然和合成抗菌肽（AMPs），也称为宿主防御蛋白/肽（HDPs），可以抑制 SARS-CoV-2，为这些分子作为治疗选择的潜在临床应用铺平了道路。在本文中，我们描述了 brilacidin 在人类肺细胞系（Calu-3）和猴细胞系（Vero）中对 SARS-CoV-2 发挥的强大抗病毒活性。这是一种从头设计的合成小分子，捕捉了 HDPs 的生物学特性。这些数据表明，在这些细胞培养模型中，SARS-CoV-2 的抑制可能是由于 brilacidin 对病毒进入的影响及其对病毒完整性的破坏。brilacidin 与 remdesivir 联合使用时表现出协同抗病毒活性。总的来说，我们的数据表明 brilacidin 对细胞培养中的不同 SARS-CoV-2 株表现出强大的抑制作用。
