基于网络药理学和分子对接探讨苦参碱抗新冠病毒机制研究  

Mechanism Study of Matrine against SARS-CoV-2 Based on Network Pharmacology and Molecular Docking

作　　者：丁园园 张荣生[1] 张冬华[1] 王轩[1] Ding Yuanyuan;Zhang Rongsheng;Zhang Donghua;Wang Xuan(Surgical oncology dept,Oncology Center of PLA,Qinhuai Medical District,Eastern Theater General Hospital of PLA&Affiliated 81st Hospitals of Nanjing University of Chinese Medicine,Nanjing 210002)

机构地区：[1]南京中医药大学附属八一医院,东部战区总医院秦淮医疗区全军肿瘤中心肿瘤外科,南京210002

出　　处：《中药药理与临床》2020年第4期18-23,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：南京军区医学科技创新课题(编号:14ZX07)。

摘　　要：目的:苦参碱(Matrine)治疗新冠肺炎(COVID-19)的临床疗效已得到了证实,但其作用机制尚不明确,因此本研究通过网络药理学和分子对接技术探究苦参碱治疗新冠肺炎的作用靶点及机制。方法:利用TCMSP、GeneCards、CTD、TTD数据库获得苦参碱治疗新冠病毒肺炎的潜在作用靶点;运用Cytoscape软件得到"靶点-通路"网络并进行拓扑学分析;使用STRING在线分析平台结合Cytoscape软件构建靶蛋白相互作用(protein-protein interaction,PPI)网络并进行拓扑学分析,继而进行GO和KEGG富集分析;最后将苦参碱与SARS-CoV-2 3CL水解酶(Mpro)、血管紧张素转化酶II(ACE2)、RNA依赖的RNA聚合酶(RdRp)进行分子对接验证。结果:共获得苦参碱-疾病共同靶点10个,分别是RELA、MMP2、TNF-α、IL-6、CASP3、MYC、ICAM1、HPSE、IER3IP1、CD44,关键靶点涉及TNF-α、IL-6和CASP3;KEGG和GO富集分析发现5条存在显著差异的信号通路以及涉及细胞增殖、细胞凋亡、细胞程序性死亡及免疫应答等生物学过程。结论:该研究初步揭示了苦参碱作用于TNF信号通路中TNF-α、IL-6和CASP3靶点调控病毒复制、细胞凋亡以及炎症反应达到治疗COVID-19的目的。Objective: The clinical efficacy of Matrine in the treatment of COVID-19 has been confirmed, however, its underlying mechanism remains unknown. This study aimed to investigate the mechanism of Matrine on COVID-19 through network pharmacology and molecular docking analyses. Methods: TCMSP, GeneCards, CTD、TTD were used to identify potential targets of Matrine treating SARS-CoV-2. Cytoscape software was used to determine the target-pathway network for topographical analysis. The online STRING analysis platform and Cytoscape were used to construct a protein-protein interaction(PPI) network, then topological analysis, Gene Ontology(GO) and KEGG pathway enrichment analysis were carried out. Finally, molecular docking verification was performed to study Matrine-SARS-CoV-2-3 CL hydrolase(Mpro), ACE2 and RNA-dependent RNA polymerase(RdRp) interactions. Results: Ten common Matrine-targets including RELA, MMP2, TNF-α, IL6, CASP3, MYC, ICAM1, HPSE, IER3 IP1, CD44 were obtained, while the key targets were TNF-α, IL-6, and CASP3. GO and KEGG pathway enrichment analysis revealed five significantly enriched signalling pathways and biological process, such as cell proliferation, apoptosis, programmed cell death, and immune responses. Conclusion: In this study, Matrine is shown to be effective against SARS-CoV-2, it may be via TNF-α, IL-6, and CASP3 targets to regulate the viral replication, host cell apoptosis, and inflammation response in TNF signalling pathway.

关 键 词：苦参碱 新冠肺炎 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]