The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells

Virulence

Cristelle Hugo¹  Theodoros Kelesidis¹  Eleni Ritou¹  Madhav Sharma¹  Orian S Shirihai¹  Anton Petcherski¹  Srinivasa T Reddy²  David S Williams³  Nan W Hultgren³  Ellen O’Connor⁴ 

[1] Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, US;Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, US;Molecular Toxicology Interdepartmental Degree Program, University of California Los Angeles, United State;Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, US;Department of Ophthalmology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, US;Molecular Toxicology Interdepartmental Degree Program, University of California Los Angeles, United State;

关键词: COVID-19;    SARS-CoV-2;    ApoA-I mimetic peptides;    4F;    therapeutics;    inflammation;    apoptosis;    antivirals;    antioxidants;   

DOI  :  10.1080/21505594.2021.1964329

来源: Taylor & Francis

【 摘 要 】

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.

【 授权许可】

CC BY