SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damage and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of the virus' excessively damaging abilities remains unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is sufficient to cause acute respiratory distress syndrome (ARD...

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Published inbioRxiv
Main Authors Gao, Zhaobing, Xia, Bingqing, Shen, Xurui, He, Yang, Pan, Xiaoyan, Wang, Yi, Yang, Feipu, Fang, Sui, Wu, Yan, Zuo, Xiaoli, Xie, Zhuqing, Jiang, Xiangrui, Chi, Hao, Meng, Qian, Hu, Zhou, Zhou, Yubo, Cheng, Xi, Cheng, Tong, Xin, Xiaoming, Jiang, Hualiang, Xiao, Gengfu, Zhao, Qiang, Lei-Ke, Zhang, Shen, Jingshan, Li, Jia
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 29.06.2020
Subjects
Cell death
Cell membranes
Chemokines
Cytokine storm
Cytokines
Intravenous administration
Macrophages
Proteins
Pyroptosis
Respiratory distress syndrome
Respiratory therapy
Severe acute respiratory syndrome coronavirus 2
Spleen
Therapeutic targets
Viral envelope proteins
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Summary:Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of the virus' excessively damaging abilities remains unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is sufficient to cause acute respiratory distress syndrome (ARDS)-like damage in vitro and in vivo. Overexpression of 2-E protein induced rapid pyroptosis-like cell death in various susceptible cells and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damage in lung and spleen. Overexpressed 2-E protein formed cation channels in host cell membranes, eventually leading to membrane rupture. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent protective effects against the 2-E-induced damage both in vitro and in vivo. Importantly, their channel inhibition, cell protection and antiviral activities were positively correlated with each other, supporting 2-E is a promising drug target against SARS-CoV-2. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.06.27.174953