基于网络药理学和分子对接的金叶败毒颗粒治疗新型冠状病毒肺炎的作用机制研究  

Mechanism Study of Jinye Baidu Granules Treating COVID-19 Based on Network Pharmacology and Molecular Docking

作　　者：王艺 张英睿 龚宇晟 石依姗 方建国[4] 张艺 Wang Yi;Zhang Yingrui;Gong Yusheng;Shi Yishan;Fang Jianguo;Zhang Yi(Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinose Medicine,Chengdu 611137;Ethnic Medicine College,Chengdu University of Traditional Chinese Medicine,Chengdu 611137;College of pharmacy,Chengdu university of traditional Chinese medicine,Chengdu 611137;Department of Pharmacy,Tongi Hospital Afiliated with Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030)

机构地区：[1]成都中医药大学民族医药学术传承创新研究中心,成都611137 [2]成都中医药大学民族医药学院,成都611137 [3]成都中医药大学药学院,成都611137 [4]华中科技大学同济医学院附属同济医院药学部,武汉430030

出　　处：《中药药理与临床》2020年第6期31-39,共9页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家重点研发计划项目(编号:2017YFC1703900);国家实验室药品监督管理局中成药质量评价重点实验室项目。

摘　　要：目的:通过网络药理学结合分子对接方法探寻金叶败毒颗粒治疗新型冠状病毒肺炎(COVID-19)的作用机制。方法:借助TCMSP及BATMAN-TCM数据库筛选金叶败毒颗粒中金银花、大青叶、蒲公英、鱼腥草的化学成分和作用靶点,通过GeneCards数据库筛选新冠肺炎的预测靶点,将两者靶点进行映射,得到金叶败毒颗粒治疗COVID-19关键靶点;通过UniProt数据库校正靶点对应的基因,进而运用Cytoscape 3.7.2构建药物-化学成分-关键靶点(基因)网络,通过String数据库绘制蛋白质相互作用网络,通过DAVID数据库对关键靶点进行GO注释和KEGG通路富集分析。采用Maestro version 11.5软件,将活性成分作为配体与受体血管紧张素转换酶II(ACE2)和SARS-CoV-23CL水解酶进行分子对接验证。结果:金叶败毒颗粒共获得349个化合物,筛选得到51个活性化合物,成分相关靶点274个,COVID-19相关靶点345个,药物-疾病的共同靶点49个。GO功能富集分析得到GO条目756个(P<0.05),其中生物过程(BP)条目688个,细胞组成(CC)条目33个,分子功能(MF)条目35个。KEGG通路富集筛选得到53个信号通路(P<0.05),涉及癌症通路、T细胞受体信号通路、Toll样受体信号通路、NOD样受体信号通路、细胞凋亡通路等。分子对接结果显示金叶败毒颗粒中靛玉红、异鼠李素、山柰酚、木犀草素等10个成分与受体结合能力较强,可能是金叶败毒颗粒治疗新型冠状病毒肺炎的潜在活性成分。结论:金叶败毒颗粒中的活性化合物可通过与受体结合作用多个靶点调节多条信号通路,对COVID-19发挥潜在防治作用。Objective:To explore the mechanism of Jinye Jiangdu granule treating COVID-19 based on molecular docking combined with network pharmacology.Methods:The chemical constituents and targets of Isatidis Folium,Lonicerae Japonicae Flos,Taraxaci Herba and Houttuyniae Herba in Jinye Baidu granules were screened by TCMSP and Batman-TCM database.Then the predicted targets of COVID-19 were screened through GeneCards database.The mapping of the two targets was carried out to obtain the key targets of Jinye Baidu granules for the treatment of COVID-19.The corresponding genes of the targets were corrected by UniProt database,and then Cytoscape 3.7.2 was used to construct the drug-chemical component-key target(gene)network.The protein interaction network was drawn through String database,the GO annotation and KEGG pathway enrichment analysis of Jinye Baidu Granules action targets were performed through DAVID database.At the same time,Maestro version 11.5 software was used to perform the molecular docking verification of active compounds(ligands)and angiotensin-converting enzyme II(ACE2)and COVID 193 CL hydrolase(receptors).Results:A total of 349 compounds were obtained from Jinye Baidu granules,and 51 active compounds were screened,including 274 composition-related targets,345 COVID-19 related targets,and 49 common drug-disease targets.GO functional enrichment analysis yielded 756 GO items(P<0.05),among which,688 were biological process(BP)items,33 were cell composition(CC)items,and 35 were molecular function(MF)items.53 signaling pathways(P<0.05)were obtained from KEGG pathway enrichment screening,involving cancer signal pathway,Toll-like receptor signaling pathway,T cell receptor signaling pathway,NOD-like receptor signaling pathway and Apoptosis pathway,etc.The molecular docking results showed that 10 components of Jinye Baidu granules,such as Indirubin,Luteolin,Isorhamnetin and Kaempferol,had the better binding capacity with receptors,which might be the potential active components of Jinye Baidu granules in the treatment of

关 键 词：金叶败毒颗粒 新型冠状病毒肺炎(COVID-19) 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]