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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
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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Semantic information from SemMedBD (by NLM)
1. envelope protei CAUSES C0035222
Subject
envelope protei
Predicate
CAUSES
Object
C0035222
2. Multiple Organ Failure CAUSES Cessation of life
Subject
Multiple Organ Failure
Predicate
CAUSES
Object
Cessation of life
3. Cytokine Storm CAUSES Cessation of life
Subject
Cytokine Storm
Predicate
CAUSES
Object
Cessation of life
4. envelope PART_OF 2019 novel coronavirus
Subject
envelope
Predicate
PART_OF
Object
2019 novel coronavirus
5. e protein CAUSES Respiratory Distress Syndrom
Subject
e protein
Predicate
CAUSES
Object
Respiratory Distress Syndrom
6. e protein INTERACTS_WITH Cations
Subject
e protein
Predicate
INTERACTS_WITH
Object
Cations
7. macrophage LOCATION_OF cytokine
Subject
macrophage
Predicate
LOCATION_OF
Object
cytokine
8. macrophage LOCATION_OF chemokine
Subject
macrophage
Predicate
LOCATION_OF
Object
chemokine
9. Cells LOCATION_OF Cell Death
Subject
Cells
Predicate
LOCATION_OF
Object
Cell Death
10. Lung LOCATION_OF Tissue damage
Subject
Lung
Predicate
LOCATION_OF
Object
Tissue damage
11. Spleen LOCATION_OF Tissue damage
Subject
Spleen
Predicate
LOCATION_OF
Object
Tissue damage
12. e protein ADMINISTERED_TO Mus
Subject
e protein
Predicate
ADMINISTERED_TO
Object
Mus
13. Dominant-Negative Mutation AFFECTS Cell Death
Subject
Dominant-Negative Mutation
Predicate
AFFECTS
Object
Cell Death
14. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
15. Lung LOCATION_OF cytokine
Subject
Lung
Predicate
LOCATION_OF
Object
cytokine
16. Lung PART_OF Mic
Subject
Lung
Predicate
PART_OF
Object
Mic
17. cytokine PRODUCES angiotensin converting enzyme 2
Subject
cytokine
Predicate
PRODUCES
Object
angiotensin converting enzyme 2
18. envelope protein, SARS-CoV-2 CAUSES Respiratory Distress Syndrome, Adult
Subject
envelope protein, SARS-CoV-2
Predicate
CAUSES
Object
Respiratory Distress Syndrome, Adult
19. Multiple Organ Failure CAUSES Cessation of life
Subject
Multiple Organ Failure
Predicate
CAUSES
Object
Cessation of life
20. Cytokine Storm CAUSES Cessation of life
Subject
Cytokine Storm
Predicate
CAUSES
Object
Cessation of life
21. envelope PART_OF 2019 novel coronavirus
Subject
envelope
Predicate
PART_OF
Object
2019 novel coronavirus
22. e protein CAUSES Respiratory Distress Syndrome, Adult
Subject
e protein
Predicate
CAUSES
Object
Respiratory Distress Syndrome, Adult
23. e protein INTERACTS_WITH Cations
Subject
e protein
Predicate
INTERACTS_WITH
Object
Cations
24. macrophage LOCATION_OF cytokine
Subject
macrophage
Predicate
LOCATION_OF
Object
cytokine
25. macrophage LOCATION_OF chemokine
Subject
macrophage
Predicate
LOCATION_OF
Object
chemokine
26. Cells LOCATION_OF Cell Death
Subject
Cells
Predicate
LOCATION_OF
Object
Cell Death
27. Lung LOCATION_OF Tissue damage
Subject
Lung
Predicate
LOCATION_OF
Object
Tissue damage
28. Spleen LOCATION_OF Tissue damage
Subject
Spleen
Predicate
LOCATION_OF
Object
Tissue damage
29. e protein ADMINISTERED_TO Mus
Subject
e protein
Predicate
ADMINISTERED_TO
Object
Mus
30. Dominant-Negative Mutation AFFECTS Cell Death
Subject
Dominant-Negative Mutation
Predicate
AFFECTS
Object
Cell Death
31. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
32. Lung LOCATION_OF cytokine
Subject
Lung
Predicate
LOCATION_OF
Object
cytokine
33. Lung PART_OF Mice, Transgenic
Subject
Lung
Predicate
PART_OF
Object
Mice, Transgenic
34. cytokine PRODUCES angiotensin converting enzyme 2
Subject
cytokine
Predicate
PRODUCES
Object
angiotensin converting enzyme 2
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.
Subject(s)

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