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

文献类型：期刊论文

作者Xia, Bingqing1,2; Shen, Xurui1,2; He, Yang1,2; Pan, Xiaoyan3; Liu, Feng-Liang4,5; Wang, Yi1,2; Yang, Feipu1,2; Fang, Sui1; Wu, Yan3; Duan, Zilei4,5
刊名CELL RESEARCH
出版日期2021-06-10
页码14
ISSN号1001-0602
DOI10.1038/s41422-021-00519-4
通讯作者Zheng, Yong-Tang(zhengyt@mail.kiz.ac.cn) ; Zhang, Lei-Ke(zhangleike@wh.iov.cn) ; Shen, Jingshan(shenjingshan@simm.ac.cn) ; Li, Jia(jli@simm.ac.cn) ; Gao, Zhaobing(zbgao@simm.ac.cn)
英文摘要Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.
WOS关键词ION-CHANNEL ACTIVITY ; SYNDROME CORONAVIRUS ; CELL ENTRY ; SARS ; COVID-19 ; MLKL ; INFLAMMASOME ; EPIDEMIOLOGY ; PNEUMONIA ; CHINA
资助项目National Science Fund of Distinguished Young Scholars[81825021] ; Fund of Youth Innovation Promotion Association[2019285] ; National Natural Science Foundation of China[81773707] ; National Natural Science Foundation of China[31700732] ; National Key R&D Program of China[2020YFC0842000] ; Strategic Leading Science and Technology Projects of Chinese Academy of Sciences[XDA12050308] ; Fund of National Science and Technology Major Project[2018ZX09711002-002-006] ; Hubei Science and Technology Project[2020FCA003]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000659829200001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/297153]  
专题新药研究国家重点实验室
通讯作者Zheng, Yong-Tang; Zhang, Lei-Ke; Shen, Jingshan; Li, Jia; Gao, Zhaobing
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Stake Key Lab Drug Res, CAS Key Lab Receptor Res, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Ctr Biosafety Mega Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China
4.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China
5.Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common, Kunming, Yunnan, Peoples R China
6.Shanghai Univ Med & Hlth Sci, Shanghai, Peoples R China
7.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Yunnan, Peoples R China
8.Chinese Acad Sci, Ctr Biosafety Mega Sci, Kunming Natl High Level Biosafety Res Ctr Nonhuma, Kunming Inst Zool, Kunming, Yunnan, Peoples R China
9.Ctr Cell Fate & Lineage CCLA, Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou, Guangdong, Peoples R China
10.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, CAS Key Lab Regenerat Biol, Guangzhou, Guangdong, Peoples R China
推荐引用方式
GB/T 7714		 Xia, Bingqing,Shen, Xurui,He, Yang,et al. SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target[J]. CELL RESEARCH,2021:14.
APA Xia, Bingqing.,Shen, Xurui.,He, Yang.,Pan, Xiaoyan.,Liu, Feng-Liang.,...&Gao, Zhaobing.(2021).SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target.CELL RESEARCH,14.
MLA Xia, Bingqing,et al."SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target".CELL RESEARCH (2021):14.

入库方式： OAI收割

来源：上海药物研究所

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