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Network pharmacology and RNA-sequencing reveal the molecular mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction.
He, Ding-Dong; Zhang, Xiao-Kang; Zhu, Xin-Yu; Huang, Fang-Fang; Wang, Zi; Tu, Jian-Cheng.
  • He DD; Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
  • Zhang XK; Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
  • Zhu XY; Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
  • Huang FF; Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
  • Wang Z; Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
  • Tu JC; Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China. Electronic address: jianchengtu@whu.edu.cn.
Comput Biol Med ; 131: 104293, 2021 04.
Article in English | MEDLINE | ID: covidwho-1101164
Semantic information from SemMedBD (by NLM)
1. 2019 novel coronavirus CAUSES Communicable Disease
Subject
2019 novel coronavirus
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CAUSES
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Communicable Disease
2. Cell Death AFFECTS Cardiac function
Subject
Cell Death
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AFFECTS
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Cardiac function
3. Myocyte LOCATION_OF C0017337
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Myocyte
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LOCATION_OF
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C0017337
4. Myocyte LOCATION_OF C1414372|1993
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Myocyte
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LOCATION_OF
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C1414372|1993
5. Myocyte LOCATION_OF C1422064|59272
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Myocyte
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LOCATION_OF
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C1422064|59272
6. Proteins INTERACTS_WITH Injection
Subject
Proteins
Predicate
INTERACTS_WITH
Object
Injection
7. Genes PART_OF Myocyte
Subject
Genes
Predicate
PART_OF
Object
Myocyte
8. Genes INTERACTS_WITH Injection
Subject
Genes
Predicate
INTERACTS_WITH
Object
Injection
9. ELAVL2 gene|ELAVL2 AUGMENTS Biochemical Pathway
Subject
ELAVL2 gene|ELAVL2
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AUGMENTS
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Biochemical Pathway
10. receptor PART_OF 2019 novel coronavirus
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receptor
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PART_OF
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2019 novel coronavirus
11. Basis INTERACTS_WITH Injection
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Basis
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INTERACTS_WITH
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Injection
12. 2019 novel coronavirus CAUSES Communicable Diseases, Emerging
Subject
2019 novel coronavirus
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CAUSES
Object
Communicable Diseases, Emerging
13. Cell Death AFFECTS Cardiac function
Subject
Cell Death
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AFFECTS
Object
Cardiac function
14. Myocytes, Cardiac LOCATION_OF Genes
Subject
Myocytes, Cardiac
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LOCATION_OF
Object
Genes
15. Myocytes, Cardiac LOCATION_OF ELAVL2 gene|ELAVL2
Subject
Myocytes, Cardiac
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LOCATION_OF
Object
ELAVL2 gene|ELAVL2
16. Myocytes, Cardiac LOCATION_OF ACE2 gene|ACE2
Subject
Myocytes, Cardiac
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LOCATION_OF
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ACE2 gene|ACE2
17. Proteins INTERACTS_WITH Injection
Subject
Proteins
Predicate
INTERACTS_WITH
Object
Injection
18. Genes PART_OF Myocytes, Cardiac
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Genes
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PART_OF
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Myocytes, Cardiac
19. Genes INTERACTS_WITH Injection
Subject
Genes
Predicate
INTERACTS_WITH
Object
Injection
20. ELAVL2 gene|ELAVL2 AUGMENTS Biochemical Pathway
Subject
ELAVL2 gene|ELAVL2
Predicate
AUGMENTS
Object
Biochemical Pathway
21. receptor PART_OF 2019 novel coronavirus
Subject
receptor
Predicate
PART_OF
Object
2019 novel coronavirus
22. Basis INTERACTS_WITH Injection
Subject
Basis
Predicate
INTERACTS_WITH
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Injection
ABSTRACT

BACKGROUND:

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Up to 20%-30% of patients hospitalized with COVID-19 have evidence of cardiac dysfunction. Xuebijing injection is a compound injection containing five traditional Chinese medicine ingredients, which can protect cells from SARS-CoV-2-induced cell death and improve cardiac function. However, the specific protective mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction remains unclear.

METHODS:

The therapeutic effect of Xuebijing injection on COVID-19 was validated by the TCM Anti COVID-19 (TCMATCOV) platform. RNA-sequencing (RNA-seq) data from GSE150392 was used to find differentially expressed genes (DEGs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. Data from GSE151879 was used to verify the expression of Angiotensin I Converting Enzyme 2 (ACE2) and central hub genes in both human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) and adult human CMs with SARS-CoV-2 infection.

RESULTS:

A total of 97 proteins were identified as the therapeutic targets of Xuebijing injection for COVID-19. There were 22 DEGs in SARS-CoV-2 infected hiPSC-CMs overlapped with the 97 therapeutic targets, which might be the therapeutic targets of Xuebijing injection on COVID-19-induced cardiac dysfunction. Based on the bioinformatics analysis, 7 genes (CCL2, CXCL8, FOS, IFNB1, IL-1A, IL-1B, SERPINE1) were identified as central hub genes and enriched in pathways including cytokines, inflammation, cell senescence and oxidative stress. ACE2, the receptor of SARS-CoV-2, and the 7 central hub genes were differentially expressed in at least two kinds of SARS-CoV-2 infected CMs. Besides, FOS and quercetin exhibited the tightest binding by molecular docking analysis.

CONCLUSION:

Our study indicated the underlying protective effect of Xuebijing injection on COVID-19, especially on COVID19-induced cardiac dysfunction, which provided the theoretical basis for exploring the potential protective mechanism of Xuebijing injection on COVID19-induced cardiac dysfunction.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Drugs, Chinese Herbal / Gene Expression Regulation / Myocytes, Cardiac / RNA-Seq / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Traditional medicine Limits: Humans Language: English Journal: Comput Biol Med Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Drugs, Chinese Herbal / Gene Expression Regulation / Myocytes, Cardiac / RNA-Seq / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Traditional medicine Limits: Humans Language: English Journal: Comput Biol Med Year: 2021 Document Type: Article