Deciphering the mechanism of Ephedra Herba-Armeniacae Semen Amarum herb pairs on COVID-19 by integrated network pharmacology and bioinformatics

Abstract

Background: Effective prevention of COVID-19 is vital for impeding the current pandemic. Our study is devoted to investigating the targets of Ephedra Herba (EH)-Armeniacae Semen Amarum (ASA) herb pairs on COVID-19 and identifying the signature genes. Methods: Firstly, the active constituents and corresponding targets of EH-ASA were separately obtained through Traditional Chinese Medicine System Pharmacology Database (TCMSP) and UniProt KB database. We searched the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) for COVID-19 and intersected the targets with DEGs to retrieve common genes. Subsequently, the Protein-Protein Interaction (PPI) network and weighted gene coexpression network analysis (WCGNA) were carried out to discover the genes related to COVID-19, which was combined with DEGs performed the GO and KEGG enrichment analysis to investigate the pathogenesis of COVID-19. The receiver operating characteristic curve (ROC) and molecular docking were ultimately exerted to verify the precision and stability of the screened genes. Results: There were 42 active compounds of the EH-ASA corresponding to 200 targets, including Luteolin, Glycyrol, Glabridin, and Quercetin. Also, 548 DEGs were filtered out, and 74 common genes were obtained after the intersection. In addition, 358 genes associated with COVID-19 were identified through the WGCNA method, mainly involved in Human T-cell leukemia virus one infection and IL-17 signaling pathway, etc. At last, three signature genes were obtained, containing ESR1, IL2, and NFKBIA, and the ROC of these three genes was 1.000, 0.967, and 0.967, respectively, which illuminated the accuracy of the results. Also, molecular docking indicated that the main chemical constituents of the EH-ASA had a good affinity with COVID-19. Conclusion: EH-ASA herb pairs may play a preventive and therapeutic role in COVID-19 through the three characteristic genes, ESR1, IL2, and NFKBIA.

Keywords

• Ephedra Herba
• Armeniacae Semen Amarum
• Network pharmacology
• Bioinformatics
• COVID-19