基于网络药理学和分子对接探讨五指毛桃汤防治COVID-19的作用机制

Study on the mechanism of Wuzhimaotao decoction in the prevention and treatment of COVID-19 based on network pharmacology and molecular docking

运用网络药理学和分子对接的思路和方法,研究五指毛桃汤预防新冠肺炎(Coronavirus disease 2019,COVID-19)的作用机制。从ETCM、TCMSP、SwissADME、SwissTargetPrediction等数据库和文献中获取五指毛桃汤各味中药的主要有效成分和作用靶点,导入Cytoscape 3.8.0软件绘制药物有效成分-靶点网络图。通过TTD、GeneCards、OMIM、DrugBank、pharmgkb等数据库筛选疾病基因,将疾病基因与靶点基因取交集,通过STRING平台构建蛋白质-蛋白质相互作用(PPI)关系图,筛选得到核心基因。利用R语言软件编辑脚本文件进行GO功能和KEGG通路分析。最后,利用AutoDock4及Pymol 2.2.0平台进行分子对接分析,预测活性化合物与关键靶点的亲和力。五指毛桃汤PPI关系图涉及7味中药、155个活性成分和749个靶基因。五指毛桃汤作用于COVID-19的核心靶点基因为信号转导和转录激活因子1(STAT1)、原癌基因酪氨酸蛋白激酶Src(SRC)、信号转导和转录激活因子3(STAT3)、丝裂原活化蛋白激酶3(MAPK3)、AKT丝氨酸/苏氨酸激酶1(AKT1)和丝裂原活化蛋白激酶1(MAPK1)。GO功能分析富集到5023条生物过程、462条细胞组成、738条分子过程;KEGG通路分析富集到173条信号通路。分子对接验证显示,活性成分槲皮素、山奈酚、环桑色烯与SRC、MAPK1、MAPK3、AKT1、STAT1等靶点基因显示出良好的结合力;环桑色烯与SARS-CoV-23Clike蛋白具有良好的结合力。五指毛桃汤关键活性成分槲皮素、山奈酚、异鼠李素等可能通过作用SRC、MAPK1、STAT3、MAPK3、AKT1、STAT1等核心靶点及SARS-CoV-23Clike蛋白,调控T细胞受体信号通路和IL-17信号通路等免疫途径,抑制病毒感染,发挥预防COVID-19的作用。

This study was conducted to reveal the mechanism of Wuzhimaotao decoction in preventing Coronavirus Disease 2019(COVID-19)by network pharmacology and molecular docking.The main effective components and their targets of Wuzhimaotao Decoction were obtained from ETCM,TCMSP,SwissADME,SwissTargetPrediction databases and published papers.Cytoscape 3.8.0 software was used to construct the effective components-targets network diagram.The disease genes were screened on TTD,GeneCards,OMIM,DrugBank,pharmgkb and other databases.The disease genes and target genes were intersected,and the protein-protein interaction(PPI)diagram was constructed by STRING platform to screen the core genes.R language software was used to edit script files for GO function and KEGG pathway analysis.Finally,molecular docking analysis was performed using AutoDock4 and Pymol 2.2.0 platforms to predict the affinity of active compounds with the key targets.The PPI diagram of Wuzhimaotao Decoction involved 7 Chinese herbs,155 active components and 749 target genes.The core target genes of Wuzhimaotao Decoction which targeting to COVID-19 were signal transduction and transcriptional activator 1(STAT1),proto-oncogene tyrosine protein kinase Src(SRC),signal transduction and transcriptional activator 3(STAT3),mitogen-activated protein kinase 3(MAPK3),AKT serine/threonine kinase 1(AKT1),mitogen-activated protein kinase 1(MAPK1).GO functional analysis enriched 5023 biological processes,462 cell components,738 molecular processes,and KEGG pathway analysis enriched 173 signaling pathways.Molecular docking verification showed that the active components quercetin,kaempferol,and cyclomorusin showed excellent binding ability to target genes such as SRC,MAPK1,MAPK3,AKT1,and STAT1.The cyclomorusin also showed good binding ability to the SARS-CoV-23Clike protein.Key active ingredients quercetin,kaempferol,isorhamnetin of Wuzhimaotao Decoction may play a role in preventing COVID-19 by acting on SRC,MAPK1,STAT3,MAPK3,AKT1,STAT1 and other core targets,as well as the SARS-CoV-23Clike protein,to regulate T cell receptor signaling pathway,IL-17 signaling pathway and inhibit viral infection.