网络药理学及分子对接法探讨三仁汤主要成分对新型冠状病毒肺炎(COVID-19)的机制研究

Mechanism of sovereign medicines in Sanren Decoction on COVID-19 based on network pharmacology and molecular docking

目的通过网络药理学及分子对接法探讨三仁汤主要成分对新型冠状病毒肺炎(COVID-19)的作用机制。方法通过中药系统药理学分析平台(TCMSP)及中医整合药理学研究平台V2.0(TCMIP V2.0)获得三仁汤君药(苦杏仁、白蔻仁、薏苡仁)全部化学成分并筛选,结合相关文献筛得主要活性成分。借助Uni Port数据库查询活性成分对应靶标蛋白,Cytoscape3.7.2构建成分-靶点网络。通过STRING网站构建PPI蛋白互作网络,运用cytoHubba分析关键子网络。CTD数据库对三仁汤君药活性成分靶蛋白进行GO、KEGG富集分析。以三仁汤君药活性成分及洛匹那韦等相关化学药物为配体,通过CB-Dock网站分别与新型冠状病毒(SARS-CoV-2)3CL水解酶进行分子对接。结果三仁汤君药共有39个活性成分,对应有效靶标168个。GO功能富集分析筛得生物学过程(BP)、细胞组成(CC)、分子功能(MF)分别为25条、14条及2条。KEGG富集筛得先天免疫系统(innate immune system)、免疫系统中的细胞因子信号转导(cytokine signaling in immune system)及白介素信号通路(signaling by interleukins)等信号通路,共36条。分子对接提示三仁汤君药活性成分白桦脂酸、枣素及齐墩果酸与SARS-CoV-23CL水解酶结合性较好,三者的Vina得分与3CLpro抑制剂洛匹那韦及Rd Rp抑制剂瑞德西韦的得分相近。结论三仁汤君药可能通过调控炎症因子,参与炎症相关信号通路,以多成分、多靶点、多途径参与COVID-19的多种生理过程,对治疗COVID-19发挥一定的干预作用,且其活性成分具有潜在抗SARS-CoV-2的可能性。

Objective To investigate the mechanism of sovereign medicines in Sanren Decoction on coronavirus disease 2019(COVID-19)through network pharmacology and molecular docking methods.Methods The main active ingredients of sovereign medicines in Sanren Decoction(Armeniacae Semen Amarum,Amomun kravanh Pierre ex Gagnep,and Coicis Semen)were obtained and screened from by TCMSP and TCMID V2.0,combined with related research.Using UniPort database to query the target proteins corresponding to the active ingredients,then a component-target network was constructed by Cytoscape 3.7.2.PPI network was constructed through the STRING website,and cytoHubba was used to analysis the key subnetworks.CTD database was used to analyze GO and KEGG enrichment of the active ingredient target proteins of Sanren Decoction.Using the active ingredients of sovereign medicines in Sanren Decoction and related chemical drugs such as lopinavir as ligands,molecular docking with the SARS-CoV-23 CL hydrolase was performed through the CB-Dock website.Results Sovereign medicines in Sanren Decoction had 39 active ingredients,corresponding to 168 target proteins.The GO enrichment analysis obtained 25 biological processes(BP)items,14 related items of cell composition(CC),and two molecular function(MF)item,respectively.KEGG enrichment screened 36 signaling pathways such as innate immune system,cytokine signaling in immune system,signaling by interleukins.The molecular docking results suggested that the active ingredients of mairin,ziziphin_qt,and oleanolic acid of sovereign medicines in Sanren Decoction had good binding energy with SARS-CoV-23 CL hydrolase,and the Vina score of them were similar to those of lopinavir(the 3 CLpro inhibitor)and remdesivir(RNA-dependent RNA polymerase inhibitor).Conclusion Sovereign medicines in Sanren Decoction may participate in inflammation-related signaling pathways by regulating inflammatory factors,regulating multiple physiological processes of the disease with multi-components,multi-targets,and multi-pathways.It plays a certain intervention role in the treatment of COVID-19 and its active ingredients have potential resistance to SARS-CoV-2.