基于网络药理学的痰热清注射液治疗(COVID-19)机制研究

Study on mechanism of Tanreqing injection on COVID-19 (COVID-19) based on network pharmacology

采用网络药理学,探讨痰热清注射液治疗新型冠状病毒肺炎作用中的靶点及信号通路,阐述其潜在的作用机制.借助GeneCards, DrugBank等数据库获取新冠肺炎潜在靶点,应用文献研究、Swiss Target Prediction、Sea、及Stitch数据库筛选痰热清注射液的成分作用靶点.利用String平台构建蛋白相互作用网络,DAVID数据库进行GO功能分析和KEGG富集分析,Cytoscape软件构建痰热清注射液主要活性成分作用于COVID-19疾病靶点的核心靶点.采用SYBYL-X软件将痰热清注射液中的血中活性成分与血管紧张素转化酶Ⅱ(PDB ID∶1R42)、 SARS-CoV-2 3CL水解酶(PDB ID:6LU7)和SARS-PLpro抑制剂(PDB ID∶3e9s)、抗病毒化药物进行分子对接实验.痰热清中药物的活性成分作用靶点149个.得到COVID-19的疾病相关靶点为439个,两者PPI后取交集并进行筛选得到80个关键靶点.对这80个关键靶点进行GO功能富集和KEGG通路富集分析,GO生物过程166条;KEGG信号通路105条.分子对接结果显示异绿原酸A、新绿原酸、异绿原酸C均能较好的与ACE2、SARS-CoV-2 3CL水解酶、SARS-PL pro结合并形成氢键.痰热清中的活性化合物可能通过抗病毒、抗炎、免疫调节、调控凋亡等作用,对COVID-19导致的感染、炎症以及肺损伤疾病产生治疗作用,研究结果可为中医药治疗COVID-19提供一定的理论基础与科学依据.

In this paper, network pharmacology was used to explore the targets and signal pathways of Tanreqing injection in the treatment of COVID-19, and to elaborate its potential mechanism of the action. Potential targets of COVID-19 were obtained by Genecards, Drugbank and other databases, and literature study, Swiss Target Prediction, SEA and Stitch database were used to screen the component action targets of tanreqing injection. Protein interaction network was constructed using the String platform, GO function analysis and KEGG enrichment analysis were performed in the David database, and the core target of the main active ingredient of Tanreqing injection acting on COVID-19 disease target was constructed by Cytoscape software.SYBYL-X software was used to conduct molecular docking experiments between the blood active components of Tanreqing injection and angiotensin converting enzyme II(PDB ID∶1 r42), SARS-CoV-2 3 CL hydrolase(PDB ID∶6 lu7), SARS-PLpro inhibitor(PDB ID∶3 e9 s) and antiviral drugs. There were 149 targets of the active ingredients in Tanreqing. A total of 439 disease-related targets of COVID-19 were obtained, and 80 key targets were obtained after the intersection of the two PPI and screening. Go function enrichment and KEGG pathway enrichment analysis were performed on these 80 key targets. There were 166 GO biological processes and 105 KEGG signaling pathways. Molecular docking results showed that 3,5-dicaffeoylquinic acid, neochlorogenic acid and 3,4-dicaffeoylquinic acid could combine well with ACE2, SARS-CoV-2 3 CL hydrolase and SARS-PLpro inhibitor to form hydrogen bonds. The active compounds in Tanreqing have therapeutic effects on COVID-19 induced infection, inflammation and lung injury diseases by antiviral, anti-inflammatory, immune regulation and apoptosis regulation. The research results can provide certain theoretical basis and scientific basis for the treatment of COVID-19 by traditional Chinese medicine.