基于网络药理学与分子对接法探讨薛氏五叶芦根汤代茶饮防控新型冠状病毒肺炎的作用机理

Study on the Mechanism of Xue’s Wuye Lugen Decoction on the Prevention and Control of COVID-19 Based on Network Pharmacology and Molecular Docking

目的探讨薛氏五叶芦根汤防控新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的网络作用机制及可行性。方法在中药系统药理学数据库及分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)检索下载薛氏五叶芦根汤所有中药的活性成分、作用靶标及分子结构;利用Cytoscape软件构建成分-靶标网络;将作用靶标导入STRING平台进行蛋白互作分析;借助R软件对靶标进行基因本体(Gene Ontology,GO)、KEGG(Kyoto Encyclopedia of Genes and Genomes)信号通路分析;在RCSB PDB(RCSBProtein Data Bank)数据库中检索获取COVID-19相关靶标的晶体结构,借助AutoDockTool、Vina软件,将受体与配体进行预处理及分子对接。结果筛选获得中药活性成分57种,作用靶标286个;通过构建成分-靶标网络获得4个核心网络;通过GO富集获得P≤0.05的生物学过程189条,主要涉及肾上腺素能受体活性、G蛋白偶联胺受体活性、核受体活性等;通过KEGG富集获得P≤0.05的信号通路100条,主要涉及糖尿病并发症中的晚期糖基化终末产物及其受体(AGE-RAGE)信号通路、乙型肝炎、白介素-17(Interleukin,IL-17)信号通路、卡波西肉瘤相关疱疹病毒感染、人巨细胞病毒感染、流体剪切应力与动脉粥样硬化、肿瘤坏死因子信号途径等;分子对接结果显示所含活性成分与COVID-19相关靶标的结合能均P<-5kcaL/mol(20.9kj/mol)。结论薛氏五叶芦根汤代茶饮的多种活性成分可通过与COVID-19的相关靶标结合,通过多种生物学途径对COVID-19发挥调控作用。

Objective To explore the network mechanism and feasibility of Xue’s Wuye Lugen decoction in the prevention and control of new coronavirus disease 2019(COVID-19).Methods Search and download the active ingredients,targets and molecular structures of all Xue’s Wuye Lugen decoctions in the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database.Constructing a component-target network using Cytoscape software;introduce target to STRING platform for protein interaction analysis;use R software to analyze target pathways of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG);the crystal structure of the COVID-19-related target was retrieved from the RCSB PDB(RCSB Protein Data Bank)database,and the receptors and ligands were pretreated and molecularly docked with the help of AutoDockTool and Vina software.Results 57 kinds of active ingredients of traditional Chinese medicine were obtained through screening,and286 targets were acting;obtain 4 core networks by constructing the component-target network;189 biological processes with P≤0.05 obtained through GO enrichment,mainly related to adrenergic receptor activity,G protein coupled amine receptor activity,nuclear receptor activity,etc;by KEGG enrichment,100 signal pathways with P≤0.05 were obtained,which mainly involved advanced glycation end products and their receptor(AGE-RAGE)signal pathways in diabetes complications,hepatitis B,and interleukin-17(IL-17)signaling pathway,Kaposi’s sarcoma-associated herpes virus infection,human cytomegalovirus infection,fluid shear stress and atherosclerosis,tumor necrosis factor signaling pathway,etc;the molecular docking results showed that the binding energies of the active ingredients and COVID-19-related targets were all less than-5 kcaL/mol(20.9 kj/mol).Conclusion A variety of active ingredients contained in Xue’s Wuye Lugen decoction can be combined with relevant targets of COVID-19 to play a role in controlling COVID-19 through various biological pathways.