Network pharmacology and RNA-sequencing reveal the molecular mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction

Comput Biol Med. 2021 Apr;131:104293. doi: 10.1016/j.compbiomed.2021.104293. Epub 2021 Feb 22.


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.

Keywords: COVID-19; Cardiac dysfunction; Molecular docking; Network pharmacology; RNA-sequencing; Xuebijing injection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / drug therapy
  • COVID-19 / metabolism*
  • Cell Line
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Human Embryonic Stem Cells / metabolism
  • Human Embryonic Stem Cells / pathology
  • Human Embryonic Stem Cells / virology
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / pathology
  • Induced Pluripotent Stem Cells / virology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Myocytes, Cardiac / virology
  • RNA-Seq*
  • SARS-CoV-2 / metabolism*


  • Drugs, Chinese Herbal
  • Xuebijing