基于网络药理学及分子对接探索金花清感颗粒辅助治疗新型冠状病毒肺炎(COVID-19)活性成分研究

Study on the Active Components in the Adjuvant Treatment of Novel Coronavirus Pneumonia (COVID-19) with Jinhua Qinggan Granules based on Network Pharmacology and Molecular Docking

目的:通过网络药理学及分子对接探寻金花清感颗粒治疗新型冠状病毒肺炎(COVID-19)的活性成分及其作用机制。方法:通过TCMSP、TCMID和BATMAN-TCM数据库检索金花清感颗粒中5种中药的成分及其作用靶点。再通过ADME(吸收、分布、代谢和排泄)参数筛选活性成分,并通过PubChem、Chemical Book、ChemDraw软件对成分进行结构确定,进行分子对接配体的构建。2019-nCoV-Mpro和ACE2作为分子对接的受体,用AutoDock软件进行分子对接。同时能与2019-nCoV-Mpro和ACE2结合的活性成分及其作用靶点通过Cytoscape 3.7.1软件构建中药-活性成分-作用靶点网络,通过String数据库对作用靶点进行蛋白相互作用分析,并得到潜在的靶点。此潜在的靶点通过ClueGO插件进行基因功能和DAVID数据进行KEGG信号通路分析。结果:分子对接结果显示金花清感颗粒中山柰酚、黄芩素和千层纸黄素A等主要活性成分与2019-nCoV-Mpro的亲和力与临床推荐化学药相似。中药-活性成分-作用靶点网络包含5个中药、10个活性成分和98个靶点。蛋白相互作用网络中筛选得到69个潜在靶点。GO基因功能分析得到与炎症反应的调节和凋亡信号通路相关基因功能(P≤0.01),KEGG信号通路分析得到PI3K-Akt信号通路和小细胞肺癌等11条信号通路(FDR≤0.01)。结论:金花清感颗粒的山柰酚、黄芩素和千层纸黄素A等活性成分可能通过与ACE2结合作用于PTGS2、BCL2和CASP3等靶点调节多条信号通路,从而可能发挥对COVID-19的治疗作用。

Objective:To explore the active components and its mechanism in the adjuvant treatment of novel coronavirus pneumonia(COVID-19)with Jinhua qinggan granule based on network pharmacology and molecular docking.Methods:Through TCMSP,TCMID and BATMAN-TCM database,the components and targets of five herbs in Jinhua qinggan granule were searched.ADME(absorption,distribution,metabolism and excretion)parameters were used to screen the active components,PubChem,Chemical Book and ChemDraw softwares were used to determine the structures of the components and construct the molecular docking ligands.2019-nCoV-Mpro and ACE2 were used as receptors for molecular docking,AutoDock software was used for molecular docking.At the same time,the active ingredients and their targets which could be combined with 2019-nCoV-Mpro and ACE2 were imported Cycloscape 3.7.1 software to construct the network of traditional Chinese medicine-active compounds-targets.The protein interaction analysis of the targets was carried out by String database,and the potential targets were obtained.This potential targets were analyzed using the Glue GO plug-in for gene function and David data for KEGG signal pathway.Results:The results of molecular docking showed that the affinity of kaempferol,baicalein and oroxylin A in Jinhua qinggan granule with 2019-nCoV-Mpro was similar to that of clinical recommended chemicals.The traditional Chinese medicine-active compounds-targets network contained 5 traditional Chinese medicines,10 active compounds and 98 targets.69 potential targets were screened from the protein interaction network.GO gene function analysis obtained the function of genes related to the regulation of inflammatory response and apoptotic signaling pathway(P≤0.01).KEGG signaling pathway analysis obtained 11 signaling pathways,including PI3 K-Akt signaling pathway and small-cell lung cancer(FDR≤0.01).Conclusion:The active components of Jinhua qinggan granule,such as kaempferol,baicalein and oroxylin A,may regulate multiple signal pathways(such as PTGS2,BCL2 and CASP3)by binding with ACE2,so as to play a therapeutic role in COVID-19.