利用网络药理学和分子对接探讨热毒宁注射液防治新型冠状病毒肺炎的作用机制  

Utilizing Network Pharmacology and Molecular Docking to Explore the Mechanism of Re Du Ning Injection in Preventing and Treating Novel Coronavirus Pneumonia

作　　者：王佰灵 郭芷彤 黄承仕 郝新才 赵永恒[1] 罗伦 WANG Bai-ling;GUO Zhi-tong;HUANG Cheng-shi;HAO Xin-cai;ZHAO Yong-heng;LUO Lun(School of Pharmacy,Shiyan,Hubei 442000,China;Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Shiyan,Hubei 442000,China;Hubei Provincial Technology and Research Center for Comprehensive Development of Medicinal Herbs,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院药学院,湖北十堰442000 [2]湖北医药学院武当特色中药研究湖北省重点实验室,湖北十堰442000 [3]湖北医药学院湖北省药用植物综合利用工程技术研究中心,湖北十堰442000

出　　处：《湖北医药学院学报》2021年第6期559-565,F0002,共8页Journal of Hubei University of Medicine

基　　金：湖北省教育厅科研计划项目(B2020104);十堰市科技局科研项目(19Y21);国家级大学生创新创业训练计划项目(202110929012);湖北省大学生创新创业项目(S202113249007)。

摘　　要：目的:利用网络药理学的方法探讨热毒宁注射液对新型冠状病毒肺炎的活性成分,并预测其作用靶点,探讨其潜在的作用机制。方法:用TCMSP、GeneCards和CTD数据库收集热毒宁注射液的活性成分及靶点,采用STRING数据库和Cytoscape软件构建药物-活性成分-靶点的网络和作用于新型冠状病毒肺炎的蛋白互作网络,通过RStudio软件中CludterProfiler包进行GO和KEGG通路的富集分析,并采用分子对接对预测结果进行验证。结果:以MW≤500、DL≥0.18和HL≥4为条件,筛选得到27个有效活性成分,包括槲皮素、木犀草素、茵陈黄酮、异鼠李素、山奈酚、异山奈素、圣草酚等,收集了90个靶点,包括JUN、AKT1、MAPK1、VEGFA和IL6等,并富集得到多条GO功能和KEGG通路,比如PI3K-Akt信号通路,IL-17信号通路,糖尿病并发症中的AGE-RAGE信号通路、MAPK信号通路,TNF信号通路,JAK-STAT信号通路,NOD样受体信号通路等。分子对接结果显示山萘酚、柽柳黄素和茵陈黄酮等与2019-nCoV 3CL水解酶具有较好的亲合力。结论:热毒宁注射液可能通过多个成分、多个靶点、多条信号通路,作用于2019-nCoV 3CL水解酶,而发挥治疗新型冠状病毒肺炎的作用。Objective The pharmacology of network was used to investigate the active ingredients of Re Du Ning injection on novel coronavirus pneumonia,and to predict its target and explore its potential mechanism.Methods Using TCMSP,Gene⁃Cards and CTD databases to collect the active ingredients and target of Re Du Ning injection,and using STRING database and Cyto-scape software to construct the network of drug active ingredients target network and the protein interaction net⁃work acting on novel coronavirus pneumonia.The enrichment analysis of GO and KEGG pathways was carried out by clus⁃terprofiler package in RStudio software,and the prediction results were verified by molecular docking.Results Under the conditions of MW≤500,DL≥0.18 and HL≥4,27 effective active ingredients were screened,including quercetin,luteo⁃lin,cylindross,isorhamnetin,kaempferol and isoxanol.We collected 90 targets,including JUN,AKT1,MAPK1,VEG⁃FA,and IL6,and enriched multiple GO functions and KEGG pathways,such as PI3K-Akt signaling pathway,IL-17 sig⁃naling pathway,AGE-RAGE signaling pathway in the complications of diabetes,MAPK signaling pathway,TNF signaling pathway,JAK-STAT signaling pathway,NOD-like receptor signaling pathway,etc.The results of molecular docking showed that kaempferol,taramoxanthin and areapillin had good affinity with the 2019-nCoV 3CL hydrolase.Conclusion Re Du Ning injection may act on the 2019-nCoV 3CL hydrolase through multiple components,multiple targets,multiple signal pathways,and play a role in the treatment of novel coronavirus pneumonia.

关 键 词：热毒宁注射液 新型冠状病毒肺炎 网络药理学 作用机制 

分 类 号：R285[医药卫生—中药学]