基于网络药理学和分子对接的感冒清热颗粒防治新型冠状病毒肺炎的作用机制  

Mechanism Exploration of Ganmao Qingre Granules in the Prevention and Treatment of Corona Virus Disease 2019 Based on Network Pharmacology and Molecular Docking

作　　者：吴倩文 赵书武 高丰 张煜 戴子琦 崔鹤蓉 陈可点 刘小靖 霍苏 王鹏龙[1] 徐意 徐冰[1] 雷海民[1] WU Qianwen;ZHAO Shuwu;GAO Feng;ZHANG Yu;DAI Ziqi;CUI Herong;CHEN Kedian;LIU Xiaojing;HUO Su;WANG Penglong;XU Yi;XU Bing;LEI Haimin(Beijing University of Chinese Medicine,Beijing 102488,China;Beijing Tongrentang Co.,Ltd.,Beijing 100062,China)

机构地区：[1]北京中医药大学,北京102488 [2]北京同仁堂科技发展有限公司,北京100062

出　　处：《世界中医药》2021年第19期2856-2863,共8页World Chinese Medicine

基　　金：国家自然科学基金项目(81173519,81603256);北京同仁堂科技发展股份有限公司委托课题(G20-01-080);新冠肺炎防控应急专项(2020-JYB-YJ-007);北京高精尖学科-系统中药学项目、中央高校基本科研经费(2020-JYB-XJSJJ-007);北京市中药基础与新药研究重点实验室项目;中国科学院青年人才培养项目(CACM-2018-QNRC2-B08)。

摘　　要：目的:基于网络药理学探索感冒清热颗粒防治新型冠状病毒肺炎(COVID-19)的药效物质基础及其作用机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)检索感冒清热颗粒中各味中药的化学成分及其作用靶点;在GeneCards数据库检索得到新型冠状病毒肺炎相关靶点;上述二者取交集,导入Cytoscape 3.7.2软件中进行处理,得到关键成分及关键靶标;再将交集靶点导入STRING数据库进行蛋白质-蛋白质相互作用(PPI)分析;利用DAVID数据库及R语言对交集靶点进行基因本体(GO)功能富集分析和京都基因和基因组百科全书(KEGG)通路富集分析;最后以感冒清热颗粒“有效成分-靶点”网络中筛选出的12个关键化合物为配体,以血管紧张转化酶2(ACE2)和SARS-CoV-23CL pro水解酶为目的受体,进行分子对接。结果:筛选出复方中化学成分共152个,相关靶点293个,其中与COVID-19共同作用的靶标有59个,与之对应有效成分共86个。核心靶点包括PTGS2、PTGS1、DPP4、F10、NOS2、TP53、TNF,关键成分包括β-胡萝卜素、槲皮素、芦丁、山柰酚、柚皮素、金合欢素、芦荟大黄素、葛根素、异鼠李素、芒柄花黄素、二氢血根碱和β-谷甾醇。应用GO富集分析得到42个GO条目,应用KEGG富集分析得到48条相关通路,其中包含细胞凋亡通路、癌症通路等。分子对接研究显示感冒清热颗粒中关键化学成分与3CL pro和ACE2的结合作用良好,甚至优于部分临床使用的药物。结论:感冒清热颗粒能通过槲皮素、芦丁、山柰酚、金合欢素和柚皮素等成分,调控细胞凋亡通路、癌症通路等,调节PTGS2、PTGS1、DPP4等蛋白的表达,来调控机体细胞生长凋亡、免疫炎症反应治疗COVID-19;同时感冒清热颗粒中的关键成分可能会通过作用于3CL pro及ACE2,来阻断新冠病毒入侵和增殖。Objective:To explore the material basis of pharmacodynamics and mechanism of Ganmao Qingre Granules in the prevention and treatment of corona virus disease 2019(COVID-19)based on network pharmacology.Methods:The chemical ingredients and drug targets of various Chinese medicines in Ganmao Qingre Granules were retrieved by Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),and the related targets of COVID-19 were retrieved in GeneCards database by using“Novel Corona Virus Pneumonia”as the key words.The common targets from the both screenings were imported into Cytoscape3.7.2 software for visualization,then the key components and key targets were obtained.Then the common targets were imported into the STRING database for protein interaction analysis.DAVID database and R language were used to perform the GO function enrichment analysis and KEGG pathway enrichment analysis of common targets.Finally,12 key compounds screened from the“herb-ingredient-target”network of Ganmao Qingre granule were selected as ligands,and angiotensin converting enzyme-related carboxypeptidase(ACE2)and SARS-CoV-23CL pro hydrolase were used as receptors for molecular docking.Results:A total of 152 chemical components and 293 related targets in the compound were screened out,among which 59 were common targets with COVID-19 and 86 corresponding active components.Core targets included PTGS2,PTGS1,DPP4,F10,NOS2,TP53,TNF,key components includedβ-carotene,quercetin,luteolin,kaempferol,naringenin,acacetin,aloe-emodin,puerarin,isorhamnetin,formononetin,dihydrosanguinarine andβ-sitosterol.42 GO entries were obtained by GO enrichment analysis,and 48 related pathways were obtained by KEGG enrichment analysis,including apoptosis pathway,cancer pathway and so on.Molecular docking studies showed that the key chemical components of Ganmao Qingre granule combined well with SARS-CoV-23CL pro hydrolase and ACE2,even better than some clinical drugs.Conclusion:Ganmao Qingre granule can regulate the apoptosis pathway,

关 键 词：感冒清热颗粒 新型冠状病毒肺炎 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]