基于网络药理学和分子对接技术探讨中药复方防治新型冠状病毒肺炎的作用机制

Discussion on Mechanism of TCM Compounds for Prevention and Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking

目的运用网络药理学和分子对接技术探讨中药复方防治新型冠状病毒肺炎(COVID-19)的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)及SwissTargetPrediction数据库获取中药复方的活性成分及靶点,在GenCLiP 3和GeneCards数据库筛选新型冠状病毒肺炎疾病靶点,与中药复方活性成分靶点取交集,构建中药-活性成分-靶点网络。通过STRING数据库及Cytoscape3.7.1软件构建蛋白相互作用(PPI)网络,通过DAVID进行GO功能与KEGG通路富集分析。采用AutoDock Vina对中药活性成分及COVID-19疾病靶点进行分子对接初步验证。结果从中药复方中筛选出163个活性成分,作用于952个靶点,其中与COVID-19相关靶点264个,获得9味药、150个活性成分和264个靶点的中药-活性成分-靶点网络。度值>15.05的关键作用靶点共72个,富集分析得到生物过程、细胞组成和分子功能共108个及20条相关通路。PPI网络显示AKT1、EGFR、HSP90AA1、PTGS2、MTOR、MAPK14、ERBB2、PIK3CA、EP300和PIK3R1起关键作用。分子对接显示,中药复方活性成分与3CL水解酶、ACE2-SARS-CoV-2 S蛋白对接打分和关键靶点的结合亲和力较好。结论中药复方的活性成分能作用于AKT1、EGFR、HSP90AA1、PTGS2、MTOR、3CL水解酶和ACE2-SARS-CoV-2 S蛋白等靶点,调节多条信号通路,发挥抗炎和免疫调节等作用,进而起到对COVID-19的防治作用。

Objective To discuss the mechanism of TCM compounds for prevention and treatment of COVID-19 using network pharmacology and molecular docking.Methods The active components and targets of TCM compounds were extracted from TCMSP and SwissTargetPrediction.The COVID-19-related disease targets were obtained from GenCLiP 3 and GeneCards database.The intersection targets were obtained with the active component targets of TCM compounds,and the TCM-active components-target network was constructed.The protein-protein interaction(PPI)network was constructed by STRING database and Cytoscape 3.7.1 software,and GO function and KEGG pathway enrichment analysis was conducted using DAVID.AutoDock Vina was used to conduct preliminary verification of molecular docking of active components of TCM and COVID-19 disease targets.Results Totally 163 active components of TCM compounds were obtained,interacted with 952 targets,of which 264 targets were related to COVID-19.The TCM-active component-target network of nine types of Chinese materia medica,150 active components and 264 targets were obtained.There were a total of 72 key targets with a degree value greater than 15.05.GO enrichment analysis showed that there were 108 biological processes,cellular components and molecular functions,which were enriched in 20 COVID-19 related pathways.AKT1,EGFR,HSP90AA1,PTGS2,MTOR,MAPK14,ERBB2,PIK3CA,EP300 and PIK3R1 played an important role in target-target interaction network.Molecular docking illustrated that the active components of the TCM compounds had good binding affinity with 3CL hydrolase,ACE2-SARS-CoV-2 S protein and key targets.Conclusion The active components of TCM compounds can act on targets such as AKT1,EGFR,HSP90AA1,PTGS2,MTOR,3CL hydrolase and ACE2-SARS-CoV-2 S protein to regulate multiple signaling pathways to play anti-inflammatory and immunomodulatory effects,thereby preventing and treating COVID-19.