柴胡-葛根治疗新型冠状病毒肺炎(COVID-19)的分子靶点和机制的网络药理学分析和分子对接

Pharmacology analysis and molecular docking of the molecular targets and mecha-nisms of Chaihu-Gegen in the treatment of new coronavirus pneumonia(COVID-19)

目的利用网络药理学和分子对接的方法,对柴胡-葛根治疗COVID-19的分子靶点和机制进行分析,为相关临床和实验研究提供参考。方法在TCMSP数据库限定过滤条件,检索柴胡-葛根的成分和靶点。在Gennecards和OMIM数据库以“novel coronavirus pneumonia”为关键词,合并检索疾病的靶点。通过R软件获取药物与疾病的共有靶点。利用cytoscape3.7.2绘制柴胡-葛根治疗COVID-19成分靶点图。通过PPI蛋白互作网络和R软件绘制靶点相互作用关系和富集图。通过FUNRICHNEW3.1.3软件对柴胡-葛根治疗COVID-19的靶点进行GO(BP、CC、MF)和KEGG分析。使用AutoDock 4.2和pymol实现槲皮素和核心靶点的分子对接和可视化处理。结果共得到柴胡-葛根有效中药成分135个,柴胡-葛根治疗COVID-19主要中药成分13个,主要来自柴胡的quercetin(槲皮素)、kaempferol(木犀草素)和葛根的formononetin(芒柄花黄素);柴胡-葛根靶点172个;COVID-19靶点253个;柴胡-葛根治疗COVID-19靶点40个,主要核心靶点为IL6、MAPK8、CASP3、IL10、CCL2;柴胡-葛根治疗COVID-19涉及BP 8条,CC 55个,MF 16个,主要分别为Immune response、Extracellular space和Cytokine activity;柴胡-葛根治疗COVID-19的KEGG通路420条,主要为Integrin-linked kinase signaling。分子对接结果显示槲皮素、木犀草素和IL6、MAPK8、CASP3有良好的结合力。结论通过网络药理学分析和分子对接,探析了柴胡-葛根治疗COVID-19的分子靶点和机制,为中医药治疗COVID-19提供临床与基础指导。

Objective To use network pharmacology and molecular docking methods to analyze the molecular targets and mechanisms of Chaihu-Gegen in the treatment of COVID-19,and to provide references for related clinical and experimental studies.Methods The filter conditions were defined in the TCMSP database to search for the components and targets of Chaihu-Gegen.In the Gennecards and OMIM databases,"novel coronavirus pneumonia"was used as the key word to merge and search for disease targets.The common targets of drugs and diseases through R software were obtained.Cytoscape 3.7.2 was used to draw the target map of Chaihu-Gegen for the treatment of COVID-19.PPI protein interaction network and R software were used to draw target interaction relationship and enrichment map.The GO(BP,CC,MF)and KEGG analysis of the targets of Chaihu-Gegen in the treatment of COVID-19 were carried out by FUNRICHNEW 3.1.3 software.AutoDock 4.2 and pymol were used to realize the molecular docking and visualization of quercetin and core target.Results A total of 135 effective Chinese medicinal ingredients of Chaihu-Gegen were obtained,and 13 main Chinese medicinal ingredients of Chaihu-Gegen for the treatment of COVID-19 were mainly derived from quercetin(Chaihu),kaempferol(Chaihu)and formononetin(Gegen).172 targets of Chaihu-Gegen and 253 targets of COVID-19 were obtained.40 targets of Chaihu-Gegen for the treatment of COVID-19 were identified and the main core targets were IL-6,MAPK8,CASP3,IL10 and CCL2.Chaihu-Gegen treatment of COVID-19 involved 8 BPs,55 CCs and 16 MFs,which were mainly immune response,extracellular space and cytokine activity.Chaihu-Gegen lobata had 420 KEGG pathways for the treatment of COVID-19,mainly integrin-linked kinase signaling.The results of molecular docking showed that quercetin,luteolin and IL-6,MAPK8 and CASP3 have good binding power.Conclusion Through network pharmacological analysis and molecular docking,the molecular targets and mechanisms of Chaihu-Gegen in the treatment of COVID-19 have been explored,which may provide clinical and basic guidance for the treatment of COVID-19 by Chinese medicine.