| SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target |
| Xia, BQ; Shen, XR; He, Y; Pan, XY; Liu, FL; Wang, Y; Yang, FP; Fang, S; Wu, Y; Duan, ZL; Zuo, XL; Xie, ZQ; Jiang, XR; Xu, L ; Chi, H; Li, SQ; Meng, Q; Zhou, H; Zhou, YB; Cheng, X; Xin, XM; Jin, L; Zhang, HL; Yu, DD; Li, MH; Feng, XL; Chen, JK; Jiang, HL; Xiao, GF; Zheng, YT; Zhang, LK; Shen, JS; Li, J; Gao, ZB
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| 2021
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| 发表期刊 | CELL RESEARCH
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| ISSN | 1001-0602
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| 卷号 | 31期号:8页码:847-860 |
| 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. |
| 收录类别 | sci
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13816
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| 专题 | 科研部门_分子免疫药理学（郑永唐）
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推荐引用方式
GB/T 7714 |
Xia, BQ,Shen, XR,He, Y,et al. SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target[J]. CELL RESEARCH,2021,31(8):847-860.
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| APA |
Xia, BQ.,Shen, XR.,He, Y.,Pan, XY.,Liu, FL.,...&Gao, ZB.(2021).SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target.CELL RESEARCH,31(8),847-860.
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| MLA |
Xia, BQ,et al."SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target".CELL RESEARCH 31.8(2021):847-860.
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