基于网络药理学和分子对接技术的藏药三味龙胆花片用于新型冠状病毒肺炎(COVID-19)的作用机制探讨

Mechanism of Tibetan Medicine Sanwei Longdanhua tablets on COVID-19 Based on Network Pharmacology and Molecular Docking Technology

目的:初步探寻藏药三味龙胆花片治疗新型冠状病毒肺炎(COVID-19)的活性化合物及作用机制。方法:通过文献及中药系统药理学分析平台(TCMSP)检索藏药三味龙胆花片中白花龙胆、甘草、蜂蜜干膏的化学成分。通过Swiss Target Prediction数据库查询化学成分对应靶点,采用Cytoscape3.7.2构建化合物-靶点网络;结合DAVID基因本体GO功能富集分析和KEGG通路富集分析,预测其作用机制;对核心成分与抗COVID-19药物靶点进行分子对接验证。结果:化合物-靶点网络包含101个化合物,共对应168个靶点。GO功能富集分析得到GO条目291个(P<0.05),其中生物过程(BP)条目186个,细胞组成(CC)条目33个,分子功能(MF)条目72个。KEGG通路富集筛选得到56条信号通路(P<0.05),涉及钙离子信号通路、花生四烯酸代谢通路、MAPK信号通路等相关信号通路。分子对接结果显示,甘草香豆酮、槲皮素、山柰酚等核心成分与抗COVID-19药物潜在作用靶点的亲和力可能较推荐用药更强。结论:藏药三味龙胆花片可通过多成分、多靶点、多通路的协同作用发挥疗效,从而起到抗COVID-19的作用。

Objective:To explore the active compounds of Tibetan medicine Sanwei Longdanhua Tablets for the treatment of COVID-19.Methods:The information of chemical constituents of white flower gentian,licorice,and honey extract in Tibetan medicine Sanwei Longdanhua Tablets were retrieved by literature search and TCMSP.The chemical component corresponding targets were queried through the Swiss Target Prediction database,and a compound-target network was constructed by Cytoscape 3.7.2.The gene ontology(GO)functional enrichment analysis and(KEGG)pathway enrichment analysis were performed by DAVID to predict its mechanism of action.Core components and anti-COVID-19 drug targets were verified by molecular docking.Results:The compound-target network contained 101 compounds,corresponding to a total of 168 targets.GO function enrichment analysis resulted in 291 GO entries(P<0.05),in which 186 were biological process(BP)entries,33 were cell composition entries(CC),and 72 were molecular function(MF)entries.The KEGG pathway was enriched and screened to obtain 56 signal pathways(P<0.05),which involved calcium signaling pathway,Arachidonic acid metabolism,MAPK signaling pathway.The molecular docking results showed that the core components of glycycoumarin,quercetin,behenylol and the potential targets of anti-COVID-19 drugs had stronger affinity than the recommended drugs.Conclusion:The Tibetan medicine Sanwei Longdanhua Tablets can exert the curative effect on COVID-19 through the synergistic effect of multiple components,multiple targets,and multiple pathways.