基于网络药理学与分子对接技术的补肺活血胶囊用于新型冠状病毒肺炎（COVID-19）恢复期治疗的分子机制研究

目的探索补肺活血胶囊用于新型冠状病毒肺炎(COVID-19)恢复期治疗的潜在作用机制,为其临床用药提供理论指导。方法通过中药系统药理学分析平台(TCMSP)、BATMAN-TCM、中国知网(CNKI)和Pubmed数据库获得补肺活血胶囊的活性成分及作用靶点;通过GeneCards数据库获取COVID-19相关靶点,并采用交集法筛选出与补肺活血胶囊活性组分作用的共同靶点,运用Cytoscape 3.7.2构建"中药-化合物-靶点"网络,并通过String数据库构建蛋白-蛋白相互作用(PPI)网络;通过DAVID数据库进行KEGG通路和GO功能富集分析,并运用R version 3.6.3软件将结果进行可视化;采用AutoDock Tools 1.5.6、AutoDock vina 1.1.2进行分子对接研究。结果从补肺活血胶囊中共筛选出潜在活性成分32个,对应靶点203个,核心化合物11个,核心靶点52个;PPI网络分析获得补肺活血胶囊干预COVID-19关键作用靶点25个;GO及KEGG富集分析得出与补肺活血胶囊治疗COVID-19作用相关的生物过程251个(P0.05),相关信号通路93条(P0.05);分子对接结果显示补肺活血胶囊核心化合物与新型冠状病毒(SARS-CoV-2)3CL水解酶和血管紧张素转化酶II(ACE2)具有较好的亲和。结论补肺活血胶囊含有的核心化合物可作用于IL6、MAPK8、PTGS2、PTGS1、NCOA2等靶点,调节多条信号通路,从而发挥对COVID-19恢复期的治疗作用。

Molecular mechanism of Bufei Huoxue Capsule on COVID-2019 based on network pharmacology and molecular docking

Objective To explore the potential mechanism of Bufei Huoxue Capsule (BHC) on coronavirus disease 2019 (COVID-19), and provide a theoretical basis for the clinical application of BHC. Methods TCMSP, BATMAN-TCM, CNKI and Pubmed databases were used to search the compounds and targets of BHC and GeneCards database was used to search the targets of COVID-19; The intersection method was used to obtain the targets related to the therapeutic effect of BHC. Cytoscape 3.7.2 software was applied for the construction of CMM-compounds-targets network map. Protein-protein interaction (PPI) network was constructed by STRING database. Gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis were conducted by DAVID. AutoDock Tools 1.5.6 and AutoDock vina 1.1.2 were used for molecular docking. Results A total of 32 potential active components were screened from BHC, corresponding to 203 targets. Among them, there were 11 core compounds and 52 core targets. PPI network analysis showed that there were 25 key targets intervening COVID-19 by BHC. A total of 251 biological processes (P<0.05) and 93 pathways (P<0.05) were obtained by GO analysis and KEGG analysis, respectively. The results of molecular docking showed that the key compounds had good affinity with SARS-CoV-2 3CL hydrolase and angiotensin converting enzyme II. Conclusion The active compounds of BHC can target IL6, MAPK8, PTGS2, PTGS1 and NCOA2 to regulate multiple signal pathways, and play a therapeutic role in the recovery period of COVID-19.