基于网络药理学和分子对接方法祛肺毒一号方治疗新型冠状病毒肺炎作用机制研究  

Study on mechanism of Qufeidu No.1 Prescription in treatment of corona virus disease 2019 based on network pharmacology

作　　者：李伟霞[1,2,3] 张书琦 贾文汇 牛璐 陈毓龙 唐进法 LI Weixia;ZHANG Shuqi;JIA Wenhui;NIU Lu;CHEN Yulong;TANG Jinfa(Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Henan University of Chinese Medicine,Zhengzhou 450046,China;Provincial and ministerial co construction Collaborative Innovation Center for Prevention and treatment of respiratory diseases with traditional Chinese Medicine of Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学第一附属医院中药临床评价技术河南省工程实验室,河南郑州450000 [2]河南中医药大学药学院,河南郑州450046 [3]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,河南郑州450046

出　　处：《药物评价研究》2021年第4期736-744,共9页Drug Evaluation Research

基　　金：河南省中医药拔尖人才培养项目。

摘　　要：目的采用网络药理学和分子对接技术探讨祛肺毒一号方治疗新型冠状病毒肺炎(COVID-19)的物质基础和潜在作用机制。方法检索祛肺毒一号方中各药味的归经,并构建药味-归经网络;在中药系统药理学分析平台(TCMSP)数据库检索并筛选祛肺毒一号方中各药味潜在活性成分,通过文献检索补充不满足上述条件但具有药理活性的成分;采用TCMSP和Swiss Target prediction数据库获取成分相关靶标,采用Genecards数据库获取COVID-19疾病靶标;运用DAVID数据库对成分和疾病共有靶标进行KEGG通路注释和GO功能富集分析;通过STRING数据库和Cytoscape3.5.1软件构建靶标蛋白互作PPI网络和成分-靶标-通路网络;采用SYBYL-X.v1.3进行分子对接验证。结果祛肺毒一号方中药味主要归经是肺经和胃经。预测和筛选得到260个成分和85个靶标,核心化合物有槲皮素、β-谷甾醇、咖啡酸、人参皂苷Rh4、甘草查尔酮A等18个,靶标主要涉及PTGS2、NOS2、MAPK14、PPARG、PTGS1等55个,PPI核心网络涉及GAPDH、TP53、MAPK3、EGFR、TNF、IL6等11个靶标。通过GO富集获得BP、MF和CC条目分别352、71和41条,获得121条(P<0.05)KEGG信号通路,核心通路有33条,主要涉及乙型肝炎、甲型流感、PI3K-Akt信号通路、丙型肝炎、HIF-1信号通路、TNF信号通路、MAPK信号通路、T细胞受体信号通路、VEGF信号通路等。驴食草酚和3’-甲氧基光甘草定与ACE2有较好的结合活性,刺果甘草查尔酮、驴食草酚和咖啡酸与3CLpro具有较好的结合活性。结论阐释了祛肺毒一号方治疗COVID-19的多靶标、多通路协同作用,为中医药治疗COVID-19提供一定的科学依据与参考。Objective To explore the material basis and potential mechanism of Qufeidu No.1 Prescription in the treatment of corona virus disease 2019(COVID-19)by network pharmacology and molecular docking technology.Methods The meridian tropism of each flavor in Qufeidu No.1 prescription was searched and drug flavor-meridian tropism network was constructed;the potential active components of Qufeidu No.1 prescription were searched and screened on traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),and the ingredients which did not meet the above conditions but with pharmacological activity were supplemented by literature search.The component-related targets were obtained by TCMSP and Swiss Target prediction database,the disease targets of COVID-19 were acquired by Genecards database;DAVID database was used to annotate the KEGG pathway and analyze the functional enrichment of GO for the common targets of components and diseases and the target protein interaction PPI network and component-target-pathway network were constructed by STRING database and Cytoscape 3.5.1 software.Sybyl-x.v1.3 software was used to verify the molecular docking,and PyMOL software was used to plot the better docking results.Results The traditional Chinese medicine in Qufeidu No.1 prescription mainly belongs to the lung meridian and stomach meridian.Through prediction and screening,260 components and 85 targets were obtained.There were 18 core compounds including quercetin,β-sitosterol,caffeic acid,ginsenoside RH4,glycyrrhizin chalcone A and 55 targets including PTGS2,NOS2,Mapk14,PPARG and PTGS1.The PPI core network involved 11 targets such as GAPDH,TP53,mapk3,EGFR,TNF and IL6 and so on.Through GO enrichment,352,71 and 41 BP,MF and CC entries respectively obtained,121(P<0.05)KEGG signal pathways were gained,of which 33 were core pathways,mainly related to hepatitis B,influenza A,PI3 K Akt signal pathway,hepatitis C,HIF-1 signal pathway,TNF signal pathway,MAPK signal pathway,T cell receptor signal pathway,VEGF signal

关 键 词：祛肺毒一号方 新型冠状病毒肺炎 网络药理学 分子对接 作用机制 驴食草酚 3'-甲氧基光甘草定 刺果甘草查尔酮 

分 类 号：R285.5[医药卫生—中药学]