基于网络药理学和分子对接探究金花清感颗粒治疗新型冠状病毒肺炎的作用机制

Mechanism of Jinhua Qinggan Granules on COVID-19 based on network pharmacology and molecular docking

采用网络药理学和分子对接方法探究金花清感颗粒(Jinhua Qinggan Granules)治疗新型冠状病毒肺炎(COVID-19)的潜在作用靶点和机制。利用TCMSP、SwissTargetPrediction、SEA和TCMID数据库筛选金花清感颗粒的活性成分及其靶点;通过OMIM和GeneCards Suite数据库平台筛选COVID-19相关靶点;使用STRING在线分析平台构建靶蛋白相互作用(protein-protein interaction,PPI)网络并进行拓扑学分析;最后使用DAVID平台对核心靶点进行GO和KEGG富集分析;将度值排名前十的化合物与血管紧张素转化酶II(ACE2)、病毒关键S蛋白(Spike protein)、TMPRSS2蛋白、SARS-CoV-2-3CL水解酶(Mpro)、RNA依赖的RNA聚合酶(RNA-dependent RNA polymerase,RdRp)进行分子对接验证。共获得228个有效成分,以及对应的720个潜在作用靶点;获得疾病相关靶点253个,并将其映射到药物潜在靶点中,获得79个共有靶点;PPI图中,经过拓扑学分析筛选获得18个核心靶点;GO和KEGG富集分析中共获得35条存在显著差异的信号通路以及274个生物学条目;分子对接提示,金花清感方中化合物与病毒关键蛋白具有较高的结合能。该研究初步揭示了金花清感颗粒多途径,多靶点治疗新冠肺炎的潜在作用机制,为该方剂的临床运用和深入研究提供科学依据。

This study aims to use network pharmacology and molecular docking methods to explore the potential targets and mechanisms of Jinhua Qinggan Granules in the treatment of COVID-19.TCMSP,SwisstargetPrediction,SEA and TCMID were used to screen the active components and targets of Jinhua Qinggan Granules;OMIM and GeneCards Suite database platforms were used to screen the COVID-19 related targets;The protein-protein interaction(PPI)network was constructed by STRING online analysis platform and topology analysis was carried out.Finally,the DAVID platform was used to carry out GO and KEGG enrichment analysis on the core targets.The binding energy of the top 10 compounds with ACE2,Spike protein,Mpro,RdRp,TMPRSS2 was verified by molecular docking.A total of 228 active components and corresponding 720 potential targets were obtained;253 disease-related targets were mapped to potential drug targets,and 79 common targets were obtained.In PPI diagram,18 core targets were selected through topology analysis.In the GO and KEGG enrichment analysis,a total of 35 signal pathways and 274 biological items with significant differences were obtained.The molecular docking indicated that the compound in Jinhua Qinggan Granules had high binding energy with the key protein of virus.This study initially revealed Jinhua Qinggan Granules in multiple pathways and targets for the treatment of COVID-19,and provided scientific evidence for its clinical application and intensive study.