基于网络药理学和分子对接探讨清热化湿抗毒方治疗COVID-19的物质基础和作用机制

The Discussion of Material Basis and Mechanism of Action of Qingre Huashi Kangdu Prescription on the Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking

目的:探寻国医大师伍炳彩所拟清热化湿抗毒方治疗新型冠状病毒肺炎(COVID-19)的潜在效应物质基础及可能的分子机制,为新型冠状病毒肺炎(COVID-19)的中医药治疗及科研提供参考。方法:借助TCMSP、Batman等数据库检索清热化湿抗毒方的中药化学成分和作用靶点。通过GeneCards、OMIM和GEO数据库筛选出COVID-19的疾病靶点。使用Cytoscape软件构建“药物-成分-靶点-疾病”网络和潜在靶点的相互作用关系,通过Metascape富集分析预测核心模块和作用机制,并用主要成分与ACE2进行分子对接。结果:挖掘出清热化湿抗毒方中202种化学成分、301个药物靶点,COVID-19相关疾病靶点360个,二者交集靶点64个,组方中主要化学成分9个,关键靶点涉及PTGS2、NOS2、PPARG、MAPK14、NOS3、RELA等,预测到3个核心模块,核心术语主要包括感染性疾病、免疫性疾病和通路、免疫和炎症通路。GO富集分析共得到条目196个,主要涉及细胞因子介导的信号通路、对氧化应激的反应、凋亡信号通路、蛋白质定位建立的调控、活性氧代谢过程等。KEGG通路富集筛选出147条信号通路,包括糖尿病并发症中的AGE-RAGE信号通路、弓形虫病、细胞凋亡、MAPK信号通路、阿米巴病、HIF-1信号通路和RIG-I样信号通路,分子对接发现木犀草素、槲皮素、黄芩素、山柰酚、刺槐素、汉黄芩素、柚皮素7种化学成分与ACE2具有较好的结合性,且槲皮素、黄芩素、山柰酚与ACE2结合得更为稳定。结论:清热化湿抗毒方具有多成分、多靶点、多通路作用COVID-19的作用。

Objective:To explore the material basis of potential effect and possible molecular mechanisms of Qingre huashi kangdu prescription proposed by Chinese medicine master Wu Bing-cai on the treatment of Corona Virus Disease 2019(COVID-19),and to provide reference for the treatment and scientific research of COVID-19 in traditional Chinese medicine.Methods:TCMSP,Batman and other databases were used to search chemical components and action targets in traditional Chinese medicines of Qingre huashi kangdu prescription.The disease targets of COVID-19 were screened out by GeneCards,OMIM,GEO databases.Cytoscape software was used to construct the“drugs-components-targets-diseases”network and the interaction relationship between potential targets.Metascape enrichment analysis was used to predict the core modules and mechanism of action,and ACE2 was docking with the main components.Results:202 kinds of chemical components and 301 drug targets in the Qingre huashi kangdu prescription were excavated,there were 360 COVID-19 related disease targets,and 64 intersections of the two.Nine main chemical components were found in the formula,and the key targets involved PTGS2,NOS2,PPARG,MAPK14,NOS3,RELA,etc.Three core modules were predicted,and the core terms mainly included infectious diseases,immune diseases and pathways,immune and inflammatory pathways.A total of 196 items were obtained by GO enrichment analysis,which mainly involved cytokine-mediated signaling pathway,response to oxidative stress,apoptosis signaling pathway,regulation of protein localization establishment,reactive oxygen metabolism,147 signaling pathways were screened out by KEGG pathway enrichment,including AGE-RAGE signaling pathway in diabetes complications,toxoplasmosis,apoptosis,MAPK signaling pathway,amoebiasis,HIF-1 signaling pathway and RIG-I-like signaling pathway.Molecular docking showed that luteolin,quercetin,baicalein,kaempferol,robinin,wogonin and naringenin had good binding abilities with ACE2,and the combination of quercetin,baicalein and kaempferol with ACE2 was more stable.Conclusion:Qingre huashi kangdu prescription treats COVID-19 through multi-components,multi-targets and multi-pathways.