基于网络药理学和分子对接探讨莪术醇抗脑心肌炎病毒的作用机制

doi:10.16431/j.cnki.1671-7236.2023.01.034

摘要/Abstract

摘要： 【目的】利用网络药理学和分子对接技术发现莪术醇抗脑心肌炎病毒（Encephalomyocarditis virus，EMCV）的作用靶点及机制。【方法】利用PharmMapper、GeneCards数据库获得莪术醇抗EMCV的相关靶点；通过Cytoscape 3.7.2软件、STRING和DAVID数据库构建靶蛋白互作（PPI）网络并筛选关键靶点，对靶点进行GO功能和KEGG通路富集分析，并构建莪术醇抗EMCV靶点-通路网络；通过AutoDock Vina 1.1.2分析莪术醇与靶蛋白的结合能及结合模式。【结果】网络药理学分析结果显示，莪术醇抗EMCV的潜在靶点有9个，其中丝裂原活化激酶14（mitogen-activated protein kinase 14，MAPK14）、信号转导与转录激活因子1（signal transducer and activator of transcription 1，STAT1）、白蛋白（albumin，ALB）、白细胞介素2（interleukin 2，IL2）可能是莪术醇抗EMCV的核心靶点，所得靶点参与C型凝集素受体信号通路、神经营养素信号通路和JAK-STAT信号通路等代谢通路，功能涉及调节炎症反应细胞因子的产生、蛋白激酶活性和药物结合等；分子对接结果显示，4种核心靶蛋白与莪术醇之间存在较强的结合能，均存在疏水形式的结合，其中ALB、STAT1和IL2与莪术醇之间还存在氢键结合。【结论】本研究结果表明，MAPK14、STAT1、ALB和IL2是莪术醇发挥抗EMCV作用的潜在靶点，本研究为莪术醇作为抗EMCV药物的研发提供理论依据和线索。

关键词: 莪术醇; 脑心肌炎病毒(EMCV); 网络药理学; 分子对接; 靶点

Abstract: 【Objective】 The purpose of this study was to discover the target and mechanism of curcumol against Encephalomyocarditis virus (EMCV) using network pharmacology and molecular docking technology.【Method】 The potential targets of curcumol against EMCV were obtained through PharmMapper and GeneCards databases.Cytoscape 3.7.2 software, STRING and DAVID databases were used to construct the target protein-protein interaction (PPI) network to screen the key targets.GO function and KEGG pathway enrichment analysis were carried out for the target proteins.Network model of curcumol anti-EMCV targets pathway was constructed.The binding energy and binding mode of curcumol with target protein were analyzed by AutoDock Vina 1.1.2.【Result】 The results of network analysis showed that there were 9 potential targets of curcumol anti-EMCV.Mitogen-activated protein kinase 14 (MAPK14), signal transducer and activator of transcription 1 (STAT1), albumin (ALB) and interleukin 2 (IL2) might be the core targets of curcumol anti-EMCV.The targets participated in metabolic pathways such as C-type lectin receptor, neurotrophin and JAK-STAT signaling pathways, and their function involved regulation of cytokine production in inflammatory response, protein kinase activity and drug binding etc.Molecular docking showed that there was strong binding energy between the four core target proteins and curcumol.There was hydrophobic binding between the core target proteins and curcumol, and there was hydrogen bond binding between ALB, STAT1 and IL2 with curcumol.【Conclusion】The results of this study indicated that, curcumol might play the anti-EMCV role by acting on the key protein of MAPK14, STAT1, ALB and IL2.This study provided theoretical basis and clues for the research and development of curcumol as an anti-EMCV drug.

Key words: curcumol; Encephalomyocarditis virus (EMCV); network pharmacology; molecular docking; target

中图分类号:

S853.74

孙盼盼, 侯震, 郝至立, 郑剑纲, 孙娜, 范阔海, 尹伟, 李宏全. 基于网络药理学和分子对接探讨莪术醇抗脑心肌炎病毒的作用机制[J]. 中国畜牧兽医, 2023, 50(1): 341-348.

SUN Panpan, HOU Zhen, HAO Zhili, ZHENG Jiangang, SUN Na, FAN Kuohai, YIN Wei, LI Hongquan. Study on Mechanism of Curcumol Against Encephalomyocarditis Virus Based on Network Pharmacology and Molecular Docking[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(1): 341-348.

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