ABSTRACT

An oral antiviral against SARS-CoV-2 that also attenuates inflammatory instigators of severe COVID-19 is not available to date. Herein, we show that the apoA-I mimetic peptide 4 F inhibits Spike mediated viral entry and has antiviral activity against SARS-CoV-2 in human lung epithelial Calu3 and Vero-E6 cells. In SARS-CoV-2 infected Calu3 cells, 4 F upregulated inducers of the interferon pathway such as MX-1 and Heme oxygenase 1 (HO-1) and downregulated mitochondrial reactive oxygen species (mito-ROS) and CD147, a host protein that mediates viral entry. 4 F also reduced associated cellular apoptosis and secretion of IL-6 in both SARS-CoV-2 infected Vero-E6 and Calu3 cells. Thus, 4 F attenuates in vitro SARS-CoV-2 replication, associated apoptosis in epithelial cells and secretion of IL-6, a major cytokine related to COVID-19 morbidity. Given established safety of 4 F in humans, clinical studies are warranted to establish 4 F as therapy for COVID-19.

摘要

迄今为止，还没有一种针对 SARS-CoV-2 的口服抗病毒药物能够减轻严重 COVID-19 的炎症刺激因素。在此，我们证明 apoA-I 模拟肽 4 F 抑制 Spike 介导的病毒进入，并对人肺上皮 Calu3 和 Vero-E6 细胞中的 SARS-CoV-2 具有抗病毒活性。在 SARS-CoV-2 感染的 Calu3 细胞中，4 F 上调干扰素途径诱导剂，例如 MX-1 和血红素加氧酶 1 (HO-1)，并下调线粒体活性氧 (mito-ROS) 和 CD147（一种宿主蛋白​​，介导病毒进入。4 F 还减少了 SARS-CoV-2 感染的 Vero-E6 和 Calu3 细胞中相关的细胞凋亡和 IL-6 的分泌。因此，4 F 可减弱体外SARS-CoV-2 复制、相关上皮细胞凋亡以及 IL-6 的分泌，IL-6 是与 COVID-19 发病相关的主要细胞因子。鉴于 4 F 对人类的安全性已得到证实，有必要进行临床研究来确定 4 F 作为 COVID-19 的治疗方法。