基于中药系统药理学研究达原饮防治新型冠状病毒肺炎的科学内涵

Compounds,Targets and Mechanisms of DayuanYin(达原饮) in Treatment of COVID-19 Based on Systems Pharmacology of Traditional Chinese Medicine

目的 基于中药系统药理学探讨达原饮治疗新型冠状病毒肺炎(coronavirus disease 2019,COVID-19,新冠肺炎)的药效成分、靶点及其作用,并阐释其科学内涵。方法 通过中药综合数据库(TCMID)检索达原饮中已知化合物(药效成分);使用中医药分子机制生物信息学分析工具预测药效成分作用靶点;使用DrugBank数据库等获取COVID-19相关靶点;采用Cytoscape 3.7.2软件及其插件对相关靶点进行富集分析,并绘制达原饮-化合物-靶点网络关系图。结果 在达原饮7味中药中检索已知结构和可信靶点的药效成分,共197个化合物;共鉴定到1602个可信靶点;达原饮靶点涵盖COVID-19的新冠状病毒进入细胞的关键基因ACE2,参与3061种生物学过程,经MCODE聚类后归为20种主要生物学过程,涵盖以与共生体、宿主相互作用、初始病毒感染等与COVID-19高度相关的生物学过程;234种细胞作用位点,经MCODE聚类主要位于顶端膜、细胞内小管、DNA聚合酶引物酶复合物、细胞质囊;具有648种分子功能,MCODE聚类显示主要为乙酰胆碱受体的活性、细胞内配体门控离子通道活性和钙释放通道活性三类;KEGG代谢通路富集分析显示,共132个信号通路被显著富集,其中,与COVID-19密切相关的疟疾和人T细胞白血病1型病毒感染信号通路被显著富集,且各个信号通路间相互联系;达原饮中黄芩可靶向ACE2,与西药及靶点对比,达原饮中7味草药通过其化合物靶向多个靶点抗病毒。结论 (1)初步明确了达原饮多靶点、多系统相互协同治疗COVID-19的基础和数据,分析了达原饮君臣佐使配伍组方特点及开达膜原,辟秽化浊的分子机制,为后期深入的基础实验和临床抗病毒药物研究提供了明确的研究方向。(2)达原饮多组分协同,驱邪扶正,标本兼治。

Objective To explore the compounds,targets and mechanism of DayuanYin(达原饮)in the treatment of corona virus disease 2019(COVID-19)based on systemic pharmacology of traditional Chinese medicine.Methods The compounds in DayuanYinwere confirmed through TCMID.The TCM molecular mechanism bioinformatics analysis tool(BATMAN-TCM)was used to predict the target of components.The targets of COVID-19 and related drugs were recorded using DrugBank and artificial literature reading.Cytoscape 3.7.2 software and its plug-ins BiNGO,ClueGO and MCODE were used to enrich the GO annotation and pathways of the related targets.Results A total of 197 compoundswith known structure and credible target were retrieved from Dayuanyin.A total of 1602 trusted targets were identified.The target of DayuanYin covered the key gene ACE2 of coronavirus entering cells,whichmainly involved in 3061 biological processes.After MCODE clustering,it was classified into 20 main biological processes highly related to COVID-19,involving interaction with symbionts,interaction with hosts,initiation of viral infection and so on.A total of 234 kinds of action sites of cells were mainly located in apical membrane,intracellular tubule,DNA polymerase primer enzyme complex and cytoplasmic sac by MCODE clustering.It had 648 kinds of molecular functions.The MCODE cluster analysis showed that there were mainly three types of activities:acetylcholine receptor activity,intracellular ligand gated ion channel activity and calcium release channel activity.The enrichment analysis of KEGG metabolic pathway showed that 132 signal pathways were significantly enriched.Among them,malaria and human T-cell leukemia virus type 1 infection signal pathways closely related to COVID-19 were significantly enriched,and each signal pathway was interrelated.Huangqi(Scutellariae Radix)in Dayuan Yin can target ACE2.Compared with western medicine and targets,seven herbs in Dayuan Yin can target multiple targets for anti-virus through their compounds.Conclusion(1)The basis and data of the multi-target and multi-system synergistic treatment of COVID-19 with Dayuan Yin were preliminarily clarified,and the characteristics of the compatibility of the monarch,minister,assistant and envoy drugs of Dayuan Yinwere analyzedas well as the molecular mechanism of eliminating pathogens between interior-exterior to eliminate turbid,which provided a clear research direction for the later in-depth basic experiment and clinical antiviral drug research.(2)Dayuan Yin is composed of multiple components,which can expel evils and strengthen the health Qi,and treat both the symptoms and the root causes.