基于网络药理学和分子对接技术探索透解祛瘟颗粒治疗新型冠状病毒肺炎的分子机制研究

Research on Molecular Mechanism of Toujie Quwen Granules for Treatment of Coronavirus Disease 2019 Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学方法和分子对接技术探讨透解祛瘟颗粒治疗新型冠状病毒肺炎(COVID-19)的潜在靶点和作用机制,为其临床应用及科研提供理论依据。方法:使用TCMSP数据库获取透解祛瘟颗粒中16味中药的主要活性成分及其靶点。借助GeneCards数据库检索并筛选COVID-19疾病靶点。成分靶点与疾病靶点映射后应用Cytoscape 3.7.2软件构建药材-活性成分-靶点调控网络。使用STRING数据库构建PPI网络并分析潜在的蛋白质功能模块。利用Metascape数据库进行GO和KEGG分析。最后采用AutoDock Vina软件进行分子对接。结果:筛选得到透解祛瘟颗粒治疗COVID-19相关的112个活性成分及56个靶点,主要活性成分为槲皮素、木犀草素、汉黄芩素、山柰酚、黄芩素等,核心靶点为PTGS2、PTGS1、DPP4、CALM1、NOS2等。潜在靶点主要参与对脂多糖的反应、细胞因子介导的信号通路、凋亡信号通路等生物学过程,主要作用于AGE-RAGE信号通路、乙型肝炎、利什曼病等信号通路。分子对接结果显示,主要活性成分与SARS-CoV-23CLpro以及ACE2的亲和作用较好。结论:透解祛瘟颗粒可能作用于病毒感染、免疫和炎症反应相关靶点及通路,以多成分、多靶点、多通路发挥对COVID-19的治疗作用,其主要活性成分具有抗SARS-CoV-2的潜在可能。

Objective:Based on network pharmacology and molecular docking technology,the potential targets and mechanism of Toujie Quwen granules in the treatment of COVID-19 were investigated,so as to provide a theoretical basis for its clinical application and scientific research.Methods:The chemical constituents and their targets of 16 traditional Chinese medicines in Toujie Quwen granules were retrieved by TCMSP database,and the target genes that corresponding to COVID-19 were searched in GeneCards database.After mapping the targets of ingredients and disease,the medicinal material-compound-target network was constructed by Cytoscape 3.7.2 software.Then protein-protein interactions(PPI)network was built by STRING database,and the potential protein function modules were analyzed.Gene ontology(GO)functional enrichment analysis and KEGG pathway enrichment analysis were conducted by Metascape platform.Finally,Autodock Vina software was used for molecular docking.Results:112 compounds and 56 corresponding targets of Toujie Quwen granules for the treatment of COVID-19 were obtained.The main active ingredients were quercetin,luteolin,wogonin,kaempferol,baicalein,etc,and the key targets included PTGS2,PTGS1,DPP4,CALM1,NOS2.Potential targets were primarily involved in the biological processes of responding to lipopolysaccharide,cytokine-mediated signaling pathway,apoptosis signaling pathway.The targets mainly acted in AGE-RAGE signaling pathway,hepatitis B,leishmaniasis and other signaling pathways.The results of molecular docking showed that the main active components had the good affinity with SARS-CoV-23CL hydrolase and ACE2.Conclusion:Toujie Quwen granules may have therapeutic effects on COVID-19 by regulating viral infection,immune and inflammation related targets and pathways,in the way of multi-component,multi-target and multi-pathway,and the active components may have potential antiviral effects on SARS-CoV-2.