[关键词]
[摘要]
目的 以网络药理学和分子对接法探索肺毒清治疗新型冠状病毒肺炎(COVID-19)活性化合物。方法 利用中药系统药理学分析平台(TCMSP)获得肺毒清中木蝴蝶、栀子及苦参3味中药相关的成分和作用靶点,通过UniProt数据库查询靶点对应的基因;采用STRING平台构建靶点PPI网络;通过DAVID进行GO(gene ontology)生物过程及KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,对核心靶点进行网络拓扑分析,运用Cytoscape 3.7.0构建成分-靶点网络,分析预测其作用机制。肺毒清中核心化合物与新型冠状病毒(SARS-CoV-2)3CL水解酶进行分子对接,同时将结合能最低的前3位化合物与血管紧张素转化酶II(ACE2)进行分子对接。结果 成分-靶点网络得到269个节点,4 204条边,其中包括槲皮素、β-谷甾醇、山柰酚等50个成分,关键靶点有JUN、AKT1、TP53、PTGS2、FOS、ESR1等。GO功能富集分析得到GO条目2 187个(P<0.05),其中生物过程(biological process,BP)条目1 877个,细胞组成(cellular component,CC)条目105个,分子功能(molecular function,MF)条目205个;KEGG富集筛选得到25条信号通路(P<0.05),主要有乙型肝炎通路、致癌通路、肿瘤坏死因子信号通路、胰腺癌、弓形虫病通路等;木犀草素(-26.78 kJ/mol)、槲皮素(-26.36 kJ/mol)、去甲脱水淫羊藿黄素(-25.94 kJ/mol)作用于SARS-CoV-2 3CL水解酶的分子对接结合能最低。结论 肺毒清的活性化合物通过作用于JUN、AKT1、TP53、PTGS2、FOS、ESR1等靶点,与ACE2结合,调节多条信号通路,对COVID-19有潜在治疗作用。
[Key word]
[Abstract]
Objective To explore the active compounds of Feiduqing in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Methods The Chinese medicine system pharmacology analysis platform (TCMSP) was used to obtain the three Chinese medicine-related components and targets of Oroxylum indicum, Gardenia jasminoides and Sophora flavescens of Feiduqing, and the genes corresponding to the targets were queried through the UniProt database. The STRING platform was used to build the target PPI network. DAVID was used to perform GO biological processes and KEGG pathway enrichment analysis was used to perform network topology analysis on core targets. Cytoscape 3.7.0 was used to construct a component-target network analysis to predict the mechanism of Feiduqing. The core active compound of Feiduqing was molecularly docked with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL hydrolase, and the first three compounds with the lowest binding energy were docked with angiotensin converting enzyme II (ACE2). Results The component-target network included 269 nodes and 4 204 edges, including 50 components such as quercetin, beta-sitosterol, kaempferol, etc, and key targets included JUN, AKT1, TP53, PTGS2, FOS, ESR1, etc. The function enrichment analysis of GO yielded 2 187 (P<0.05), including 1 877 biological process (BP) entries, 105 cellular components (CC) entries, and 205 molecular functions (MF) entries. Twenty-five signal pathways were screened by KEGG enrichment analysis (P<0.05), mainly including hepatitis B, pathways in cancer, TNF signaling pathway, pancreatic cancer, toxoplasmosis pathway, etc. The active ingredients with the lowest molecular docking binding energy acting on SARS-CoV-2 3CL hydrolase were luteolin (-26.78 kJ/mol), quercetin (-26.36 kJ/mol), 8-prenyl-kaempferol (-25.94 kJ/mol). Conclusion The active compound of Feiduqing may have a therapeutic effect on COVID-19 through the action on targets such as JUN, AKT1, TP53, PTGS2, FOS, ESR1, binding with angiotensin converting enzyme II (ACE2) and regulating many signaling pathways.
[中图分类号]
R285
[基金项目]
四川省科学技术厅2020年省级科技计划项目(20YYJC1839);2020年成都龙泉驿区科技计划项目(新型冠状病毒感染的肺炎疫情防控专项)