通过网络药理学和分子对接研究板蓝根治疗新型冠状病毒肺炎的潜在作用机制

Research on the potential mechanism of Banlangen in the treatment of COVID-19 via network pharmacology and molecular docking

目的:应用网络药理学及分子对接预测板蓝根治疗新型冠状病毒肺炎的有效性和潜在机制。方法:从TCMSP数据库和文献研究中获得板蓝根的活性成分及潜在靶点;通过Gene Cards数据库检索新型冠状病毒肺炎相关靶点基因,并得到活性成分作用靶点和新型冠状病毒肺炎相关靶点基因的交集靶点,然后利用STRING数据库构建蛋白相互作用网络;使用Cytoscape3.8.2软件进行PPI网络可视化,通过MCODE插件提取核心靶点;在DAVID数据库对核心靶点进行GO和KEGG通路富集分析;采用分子对接模拟,验证药物和靶标结合力。结果:共筛选出板蓝根的活性成分51个,对应210个靶点,与新型冠状病毒肺炎交集靶点共65个,得到34个核心靶点;经过网络分析和分子对接结果,11个靶点(PTGS2、RELA、TNF、NOS2、IL6、CASP3、MAPK14、IFNG、IL1B、TGFB1和CASP8)被认为是具有较好对接亲和力的主要治疗靶点;富集分析结果表明,其潜在机制主要集中在与免疫炎症、抗病毒和促凋亡相关的GO生物过程和KEGG通路上。此外,PI3K-AKT信号通路被认为可能是关键通路。结论:该研究表明,板蓝根多种有效成分以协同方式与多靶点、多途径相互作用,通过调节免疫炎症、促凋亡和抗病毒功能对新型冠状病毒肺炎起作用。

Objective: To predict the effectiveness and underlying molecular mechanism of Banlangen in COVID-19 treatment through network pharmacology and molecular docking. Method: The active compounds and potential targets of Banlangen were obtained from the TCMSP database and literature research. The target genes associated with COVID-19 were retrieved through the GeneCards database, and the overlapping targets of the targets of active ingredients and COVID-19-related target genes were obtained to construct a protein-protein interaction(PPI) network through the STRING database. Cytoscape3.8.2 software was used for PPI network visualization, and the core targets were extracted by MCODE plug-in. GO and KEGG pathway enrichment analysis was performed for the core targets in the DAVID database. Molecular docking simulation was used to verify the binding ability of drugs and targets. Result: 1A total of 51 components of Banlangen were screened, corresponding to 210 targets, and 65 overlapping targets with COVID-19 as well as 34 key targets were obtained.According to network analysis and molecular docking results, 11 targets(PTGS2, RELA, TNF, NOS2, IL6, CASP3, MAPK14, IFNG,IL1B, TGFB1 and CASP8) were recognized as the main therapeutic targets with good docking affinities. The results of enrichment analysis demonstrated that the underlying mechanism was mainly focused on the GO biological processes and KEGG pathways related to immune inflammation, antiviral and pro-apoptosis. In addition, the PI3K-Akt signaling pathway was suggested to be potentially the key pathway.Conclusion: The study shows that multiple active components of Banlangen interact with multiple targets and pathways in a synergistic manner, and play a role in COVID-19 treatment by regulating immune inflammation, pro-apoptosis and antiviral functions.