摘要
目的:利用网络药理学及分子对接技术探讨四季抗病毒合剂治疗新型冠状病毒肺炎(COVID-19)的作用机制,为临床应用提供理论依据。方法:应用TCMSP数据库获得四季抗病毒合剂的活性成分及靶点,通过GeneCards数据库检索新型冠状病毒肺炎靶点,采用Cytoscape 3.6.1软件构建"中药-成分-靶点"网络,将药物及疾病的交集靶点导入STRING平台构建蛋白相互作用(PPI)网络,并利用DAVID数据库、R软件(ggplot2包)实现基因本体(GO)富集和KEGG通路富集分析,最后将四季抗病毒合剂的主要活性成分及目前临床报道有效化学药(氯喹、利巴韦林、瑞德西韦)与SARS-CoV-23CL水解酶进行分子对接。结果:经数据库分析筛选出四季抗病毒合剂活性成分156个,对应靶点271个;筛选出新型冠状病毒肺炎靶点259个,PPI网络分析获得四季抗病毒合剂干预COVID-19关键作用靶点53个,关键靶点涉及IL-6、MAPK3、TNF、MAPK8等。GO及KEGG富集分析得出与四季抗病毒合剂治疗COVID-19作用相关的生物过程499个(P<0.05),其中生物学过程条目406个、细胞组成条目38个、分子功能条目为55个;相关信号通路120条(P<0.05),主要涉及查加斯病(美洲锥虫病)、乙型肝炎、TNF信号通路、利什曼病、百日咳等通路。分子对接结果表明四季抗病毒合剂主要活性成分与SARS-CoV-23CL水解酶具有较好的亲和力且亲和力与目前临床报道有效化学药相近。结论:四季抗病毒合剂主要活性成分能稳定与SARS-CoV-23CL水解酶结合,通过多成分、多靶点调节多条信号通路发挥对COVID-19的治疗作用。
Objective:Network pharmacology and molecular docking technology were used to explore the mechanism of four Seasons antiviral mixture in the treatment of COVID-19(COVID-19),so as to provide its theoretical basis for clinical application.Methods:The active components and targets of the Four Seasons Antiviral Mixture were obtained by TCMSP database,and the COVID-19 targets were retrieved by GeneCards database.Then Cytoscape 3.6.1 software was used to construct the Chinese medicine-component–target network.Then,the intersection targets of drugs and diseases were introduced into STRING platform to construct protein-protein interaction(PPI)network,and gene ontology(GO)enrichment and KEGG pathway enrichment analysis were performed using DAVID database and R software(ggplot2 package).Finally,the main active components of the Four Season Antiviral Mixture and the currently reported effective chemical drugs(chloroquine,ribavirin,reddisivir)were combined with SARS-CoV-23 CL hydrolase for molecular docking.Results:156 active components of four Seasons Antiviral Mixture were selected by database analysis,corresponding to 271 targets.259 COVID-19 targets were screened out,and PPI network analysis obtained 53 key targets for the intervention of COVID-19 by Four Seasons Antiviral mixture,including IL6,MAPK3,TNF and MAPK8.GO and KEGG enrichment analysis showed that 499 biological processes were related to the treatment of COVID-19 by the four Seasons antiviral mixture(P<0.05),including 406 biological processes,38 cell composition and 55 molecular function.There were 120 related signaling pathways(P<0.05),mainly involving chagas disease(American trypanosomiasis),hepatitis B,TNF signaling pathways,leishmaniasis,pertussis and other pathways.The molecular docking results showed that the main active components of the Four Seasons Antiviral Mixture had a good affinity with 2019-nCoV 3 CL hydrolase and the affinity was similar to that of the effective chemical drugs reported in clinical reports.Conclusion:The main active components of
作者
杨起江
张思思
苗云波
阮丽波
杨天睿
Yang Qijiang;Zhang Sisi;Miao Yunbo;Ruan Libo;Yang Tianrui(Medical School of Kunming University of Science and Technology,Kunming,Yunnan 650000;First Peopled Hospital of Yunnan Province,Kunming 650000)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2020年第6期11-17,共7页
Pharmacology and Clinics of Chinese Materia Medica
基金
云南省基础研究计划[编号:2019FE001(-128)]。