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

By Bingqing Xia, Xurui Shen, Yang He, Xiaoyan Pan, Yi Wang, Feipu Yang, Sui Fang, Yan Wu, Xiaoli Zuo, Zhuqing Xie, Xiangrui Jiang, Hao Chi, Qian Meng, Hu Zhou, Yubo Zhou, Xi Cheng, Tong Chen, Xiaoming Xin, Ruotian Jiang, Gengfu Xiao, Qiang Zhao, Lei-Ke Zhang, Jingshan Shen, Jia Li, Zhaobing Gao

Posted 29 Jun 2020
bioRxiv DOI: 10.1101/2020.06.27.174953

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.

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