基于网络药理学方法预测维血宁合剂防治新型冠状病毒肺炎的活性成分及潜在靶点

Prediction of Active Components and Potential Targets of Weixuening Mixture for the Treatment of Novel Coronavirus Pneumonia Based on Network Pharmacology

目的:利用中药网络药理学和分子对接技术探讨维血宁合剂防治新型冠状病毒肺炎(COVID⁃19)的潜在活性成分及其作用机制。方法:借助TCMSP数据库检索维血宁合剂中所含的主要化学成分及其作用靶点,并与冠状病毒感染相关的靶点进行叠加分析,筛选维血宁合剂潜防治COVID⁃19的靶点;通过Cytoscape软件构建药材⁃活性成分⁃靶点网络;通过DAVID数据库对活性成分靶点进行基因本体(GO)和KEGG(Kyoto Encyclopedia of Genes and Genomes)通路富集分析;最后运用分子对接技术虚拟筛选维血宁合剂中活性成分与2019⁃nCoV S蛋白、人ACE2蛋白及2019⁃nCoV 3CL水解酶(3CLpro)的作用,预测维血宁合剂潜在的抗2019⁃nCoV成分。结果:从维血宁合剂中共梳理得到326个成分及555个相关靶点,其中101个成分对应的35个靶点与COVID⁃19密切相关;靶点通路富集分析表明,维血宁合剂主要作用于感染性疾病、炎症反应及免疫调节等过程。分子对接结果显示16个成分与S蛋白、ACE2及3CLpro均显示了较好的结合作用,成分类型主要为甾体、脂肪酸和酚类。结论:维血宁合剂可能主要通过调节机体免疫和炎症反应等,从而对COVID⁃19发挥潜在的防治作用。

Objective:To explore the potential active ingredients and mechanism of action of Weixuening mixture in the prevention and treatment of novel coronavirus pneumonia(COVID⁃19)by using the network pharmacology and molecular docking technology.Methods:The main chemical components and targets in Weixuening mixture were collected by using TCMSP database,the overlay analysis of targets was performed by comparing with disease targets of coronavirus infection.The herbs⁃active ingredients⁃targets network was constructed using Cytoscape software,the DAVID database was used to perform gene ontology(GO)and KEGG pathway enrichment analysis.The molecular docking technology was used to virtually screen the effects of active ingredients in Weixuening mixture and 2019⁃nCoV S protein,human ACE2 protein and 2019⁃nCoV 3CL hydrolase(3CLpro),the potential anti⁃2019⁃nCoV components of Weixuening mixture were predicted.Results:A total of 326 components and 555 related targets were combed out from Weixuening mixture.Among them,35 targets corresponding to 101 components were closely related to COVID⁃19.The analysis of target pathway enrichment showed that Weixuening mixture mainly acted on infectious diseases,inflammatory response and immune regulation.The molecular docking results indicated that the 16 components showed good binding effects with S protein,ACE2 and 3CLpro.The component types were mainly steroids,fatty acids and phenols.Conclusion:Weixuening mixture may play a potential role in preventing and treating COVID⁃19 via regulating the immune and inflammatory responses.