Mechanism of Shenfu Decoction in the treatment of critically ill patients with Coronavirus Disease 2019 (COVID-19) based on network pharmacology

摘要

Objective:The purpose of this thesis is to explore the mechanism of ShenFu Decoction in the treatment of critically ill patients with COVID-19 based on network pharmacology.Methods:The primary active ingredients and potential targets of ShenFu Decoction were searched from the TCMSP database.The targets of COVID-19 were obtained by searching the GeneCards and OMIM databases.A ShenFu Decoction-compound-target-COVID19 network and a protein-protein interaction(PPI)network were respectively constructed through the Cytoscape 3.5.1 software and the STRING database.Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed via Bioconductor bioinformatics software package and R programming language.Results:ShenFu Decoction contains 255 compounds and 94 potential targets.43 primary active ingredients were searched from the TCMSP database with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18 as the retrieval condition.Numbers of targets of COVID-19 were 352 by searching the GeneCards and the OMIM databases.16 key targets were acquired by intersecting the targets of drug with the targets of disease.There were 49 GO terms and 102 pathways after analyzing GO and KEGG.Conclusion:Kaempferol,ginsenoside rh2,beta-sitosterol,Stigmasterol and Deoxy andrographolide might be the main active ingredients which may cause the inhibition of the SARS-CoV-23CL hydrolase activity and regulate ACE2.As a result,the antiviral effect,immunoregulation,targeting cytokine storm of SFD may play an important role in the treatment of critically ill patients with COVID-19 through regulating multiple signaling pathways such as AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,C-type lectin receptor signaling pathway,HIF-1 signaling pathway.