基于2019-nCoV 3CL Mpro筛选祛肺毒一号方的活性成分及其治疗COVID-19的分子机制  

Screening of Active Ingredients of Qufeidu No.1 Recipe Based on 2019-nCoV 3CL Mpro and Its Molecular Mechanism in Treatment of COVID-19

作　　者：孙洁 蒋士卿[2] SUN Jie;JIANG Shiqing(Jiaozuo Maternal and Child Health Hospital,Jiaozuo Henan China 454000;Henan University of Chinese Medicine,Zhengzhou Henan China 450046)

机构地区：[1]焦作市妇幼保健院,河南焦作454000 [2]河南中医药大学,河南郑州450046

出　　处：《中医学报》2022年第5期1049-1058,共10页Acta Chinese Medicine

基　　金：河南省科技攻关计划项目(082102310028,212102311125)。

摘　　要：目的:基于2019-nCoV冠状病毒3CL水解酶(3CL protease,Mpro)的三维结构,采用分子对接技术和网络药理学方法探寻祛肺毒一号方治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)的物质基础和作用机制。方法:采用中药系统药理学数据库与分析平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)及文献检索搜集祛肺毒一号方组方中药的化学成分,并以类药性(drug likeness,DL)≥0.18及口服生物利用度(oral bioavailability,OB)≥30%为标准进行筛选,采用分子对接技术将筛选出的化合物与2019-nCoV 3CL Mpro对接,以结合能小于-9 kcal·mol^(-1)为标准,筛选祛肺毒一号方的活性成分。运用SwissTargetPrediction数据库预测活性成分的作用靶点,并在人类基因数据库(the human gene database,GeneCards)、美国国立生物技术信息中心(national center for biotechnology information,NCBI)数据库及CTD数据库检索COVID-19相关靶点,采用venny 2.1软件得到活性成分作用靶点与COVID-19相关靶点的交集靶点。将交集靶点导入STRING 11.0数据库,最终获得蛋白质相互作用网络图。采用DAVID数据库对交集靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。运用Cytoscape3.7.2软件构建“中药活性成分-疾病-通路-靶点”网络图。结果:通过检索TCMSP数据库与文献查找筛选出220个祛肺毒一号方的化学成分,以结合能≤-9 kcal·mol^(-1)为标准筛选得到33个活性成分,且结合能最低的3个化合物可共同作用于靶蛋白2019-nCoV 3CL Mpro。33个祛肺毒一号方活性成分的728个靶点与4165个COVID-19疾病相关靶点进行映射,最终得到祛肺毒一号方治疗COVID-19的有效靶点347个,核心靶点基因筛选得到CCR1、HCRTR2、MAPK3、BCL2L1等11个核心基因。KEGG通路富集显示靶点显著富集于磷酯酰肌醇3-�Objective:Based on the three-dimensional structure of 2019-nCoV coronavirus 3CL protease(Mpro),using molecular docking technology and network pharmacology methods to explore the treatment of new coronavirus pneumonia(corona virus disease 2019(COVID-19).Methods:The traditional chinese medicine systems pharmacology database and analysis platform(TCMSP)and literature search were used to collect the chemical constituents of traditional Chinese medicines in Qufeidu No.1.Screening was based on the criteria of drug likeness(DL)≥0.18 and oral bioavailability(OB)≥30%and molecular docking technology was used to dock the screened compounds with 2019-nCoV 3CL Mpro,with binding energy less than-9 kcal·mol^(-1) as the standard,to collect the active ingredients of Qufeidu No.1 formula.Use the SwissTargetPrediction database to predict the target of the compound,and search for COVID-19 related targets in the human gene database(GeneCards),the National Center for Biotechnology Information(NCBI)database and the CTD database,using Venny 2.1 software to obtain intersection targets.The intersection targets were imported into the STRING 11.0 database,and the protein interaction network map was finally obtained.The DAVID database was used to perform Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signal pathway enrichment analysis for the intersection targets.The"drug-ingredient-disease-target"network map was constructed using Cytoscape 3.7.2 software.Results:The chemical constituents of 220 Qufeidu No.1 recipes were screened by searching the TCMSP database and literature search,and 33 active constituents were screened based on the binding energy≤-9 kcal·mol^(-1),and the three compounds with the lowest binding energy could be selected.Co-act on target proteins to inhibit 2019-nCoV 3CL Mpro.728 targets of the active ingredients of 33 Qufeidu No.1 were mapped with 4,165 COVID-19 disease-related targets,and finally 347 effective targets of Qufei du No.1 Kecipe for the treatment of CO

关 键 词：COVID-19 祛肺毒一号方 2019-nCoV 3CL Mpro 分子对接 网络药理学 

分 类 号：R284.2[医药卫生—中药学]