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SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target.
Xia, Bingqing; Shen, Xurui; He, Yang; Pan, Xiaoyan; Liu, Feng-Liang; Wang, Yi; Yang, Feipu; Fang, Sui; Wu, Yan; Duan, Zilei; Zuo, Xiaoli; Xie, Zhuqing; Jiang, Xiangrui; Xu, Ling; Chi, Hao; Li, Shuangqu; Meng, Qian; Zhou, Hu; Zhou, Yubo; Cheng, Xi; Xin, Xiaoming; Jin, Lin; Zhang, Hai-Lin; Yu, Dan-Dan; Li, Ming-Hua; Feng, Xiao-Li; Chen, Jiekai; Jiang, Hualiang; Xiao, Gengfu; Zheng, Yong-Tang; Zhang, Lei-Ke; Shen, Jingshan; Li, Jia; Gao, Zhaobing.
  • Xia B; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Shen X; University of Chinese Academy of Sciences, Beijing, China.
  • He Y; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Pan X; University of Chinese Academy of Sciences, Beijing, China.
  • Liu FL; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Wang Y; University of Chinese Academy of Sciences, Beijing, China.
  • Yang F; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Fang S; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Wu Y; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Duan Z; University of Chinese Academy of Sciences, Beijing, China.
  • Zuo X; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Xie Z; University of Chinese Academy of Sciences, Beijing, China.
  • Jiang X; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Xu L; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Chi H; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Li S; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Meng Q; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Zhou H; Shanghai University of Medicine & Health Sciences, Shanghai, China.
  • Zhou Y; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Cheng X; University of Chinese Academy of Sciences, Beijing, China.
  • Xin X; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Jin L; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Zhang HL; University of Chinese Academy of Sciences, Beijing, China.
  • Yu DD; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Li MH; University of Chinese Academy of Sciences, Beijing, China.
  • Feng XL; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Chen J; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Jiang H; University of Chinese Academy of Sciences, Beijing, China.
  • Xiao G; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Zheng YT; University of Chinese Academy of Sciences, Beijing, China.
  • Zhang LK; CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Shen J; University of Chinese Academy of Sciences, Beijing, China.
  • Li J; Shanghai University of Medicine & Health Sciences, Shanghai, China.
  • Gao Z; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
Cell Res ; 31(8): 847-860, 2021 08.
Article in English | MEDLINE | ID: covidwho-1387284
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ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Respiratory Distress Syndrome / Coronavirus Envelope Proteins / SARS-CoV-2 / COVID-19 Topics: Long Covid Limits: Animals / Humans Language: English Journal: Cell Res Year: 2021 Document Type: Article Affiliation country: S41422-021-00519-4

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Respiratory Distress Syndrome / Coronavirus Envelope Proteins / SARS-CoV-2 / COVID-19 Topics: Long Covid Limits: Animals / Humans Language: English Journal: Cell Res Year: 2021 Document Type: Article Affiliation country: S41422-021-00519-4