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. GRAPHICAL ABSTRACT
【저자키워드】 COVID-19, SARS-CoV-2, Apoptosis, Inflammation, Therapeutics, antivirals, antioxidants, ApoA-I mimetic peptides, 4F, 【초록키워드】 severe COVID-19, Antiviral, spike, IL-6, peptide, cytokine, in vitro, antiviral activity, viral entry, CD147, heme, humans, human lung, morbidity, pathway, epithelial, SARS-CoV-2 replication, cellular, clinical study, Inflammatory, epithelial cell, mitochondrial, secretion, host protein, Calu3, Vero-E6 cells, inducer, CaLu3 cells, VERO-E6, inhibit, reduced, upregulated, the interferon, downregulated, reactive oxygen specy, attenuate, therapy for COVID-19, 【제목키워드】 peptide, in vitro, oxidative stress, epithelial cell, replication of SARS-CoV-2, attenuate,