基于网络药理学探究化湿败毒方治疗新型冠状病毒肺炎的分子机制

The Molecular Mechanism of Treating COVID-19 with Huashi Baidu Formula based on Network Pharmacology

目的:运用网络药理学及分子对接探讨化湿败毒方治疗新型冠状病毒肺炎(COVID-19)的药效基础与作用机制,为中医药治疗COVID-19提供依据。方法:通过TCMSP数据库筛选出化湿败毒方的化学成分和潜在靶标;通过Gene Cards数据库获取COVID-19的疾病靶点;继而运用Cytoscape 3.7.2软件绘制化湿败毒方"药物-成分-靶点-疾病"的作用网络及潜在靶点的相互作用关系,并进行GO和KEGG的通路分析。最后将化湿败毒方的主要活性成分与新型冠状病毒3CL水解酶(Mpro)、血管紧张素转化酶Ⅱ(ACE2)进行分子对接验证。结果:化湿败毒方中的138个活性成分,主要通过调节IL6、MAPK3、MAPK8、CASP3、IL10、MAPK1、CCL2、IL2等59个关键靶点参与COVID-19的治疗,共涉及1 751个生物学过程、27个细胞组分、82个分子功能及153条信号通路,如IL-17信号通路、NF-κB信号通路、Toll样受体信号通路、肾素-血管紧张素系统等。分子对接结果显示在化湿败毒方中,与Mpro结合最好的是黄芩素;与ACE2结合最好的为甘草酚。结论:化湿败毒方治疗新型冠状病毒肺炎具有"多成分-多靶点-多通路"的综合调节特点,其治疗重症患者的作用机制主要与干预"RAS通路-细胞因子风暴-重症危象"相关。

Objective: To explore the pharmacodynamic basis and mechanism of Huashi baidu formula in the treatment of Corona Virus Disease 2019(COVID-19)by network pharmacology and molecular docking, so as to provide evidence for the treatment of COVID-19 by TCM.Methods: The chemical constituents and potential targets of Huashi baidu formula were screened by TCMSP database.The disease targets of COVID-19 were screened by the Gene Cards database;Cytoscape 3.7.2 software was used to construct the "drugs-components-targets-diseases" interaction network of Huashi baidu formula and potential target interactions.GO and KEGG pathway analyses were carried out.At last, the main active compounds of the Huashi baidu formula were verified by molecular docking with 3 CL hydrolase(Mpro)and angiotensin conversion enzyme Ⅱ(ACE2)of 2019-nCoV.Results: 138 active compounds in Huashi baidu formula were mainly involved in the treatment of COVID-19 by regulating 59 key targets, such as IL6,MAPK3,MAPK8,CASP3,IL10,MAPK1,CCL2,IL2 and so on, related with a total of 1 751 biological processes, 27 cell components, 82 molecular functions and 153 signaling pathways, such as IL-17 signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, renin-angiotensin system, etc.The results of molecular docking showed that baicalein in Huashi baidu formula was the best combination with Mpro and the best combination with ACE2 was licorice phenol.Conclusion: Huashi baidu formula has the characteristics of comprehensive regulation of "multi-components-multi-targets-multi-pathways" in the treatment of COVID-19,and the mechanism in the treatment of critically ill patients is mainly related to the intervention of "RAS pathway-cytokine storm-severe crisis".