基于网络药理学和分子对接法研究六堡茶干预COVID-19的活性成分

周丹水; 陈小雪; 吴志敏; 倪维鞠; 邱瑞瑾; 于翠平; 蓝伦礼; 王颖芳; 陈守登; 曾宇

doi:10.11665/j.issn.1000-5048.20200507

基于网络药理学和分子对接法研究六堡茶干预COVID-19的活性成分

1.
广东药科大学中药学院，广州 510006
2.
中山大学附属第五医院广东省生物医学影像重点实验室，珠海 519000
3.
梧州市农业科学研究所，梧州市六堡茶研究院，梧州 543002
4.
桂林医学院药学院，桂林 541199

基金项目: 广西重点研发计划资助项目（No.AB1850019）

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出版历程
- 收稿日期: 2020-04-16
- 修回日期: 2020-05-21
- 刊出日期: 2020-10-24

Potential active compounds of Liupao tea for prevention and treatment of COVID-19 based on network pharmacology and molecular docking

Funds: This study was supported by the Key Research and Development Program of Guangxi Province (No.AB1850019)

摘要

摘要: 采用网络药理学和分子对接法探究六堡茶干预COVID-19的物质基础和作用机制。通过文献与中药系统药理数据库和分析平台（TCMSP）等数据库，检索得到六堡茶的化学成分并对其进行筛选得到六堡茶活性成分及对应靶标，并将对应靶标导入Uniprot数据库中进行基因名的校正，运用Cytoscape 3.7.1软件构建“六堡茶－成分－靶标”网络。通过GeneCards数据库对COVID-19疾病靶点进行预测。将六堡茶与疾病的靶标进行映射，采用STRING数据库分析靶标蛋白的互作关系，从中筛选出核心靶标并运用DAVID等数据库对核心靶标进行GO（gene ontology）富集分析和KEGG （kyoto encyclopedia of genes and genomes）通路富集分析。最后将筛选出来的活性成分与受体蛋白SARS-CoV-2 3CL水解酶（M^pro）进行分子对接。筛选得到6种六堡茶活性成分，分别是（+）-儿茶素、（-）-表没食子儿茶素没食子酸酯（EGCG）、α-菠甾醇、（-）-儿茶素没食子酸酯、角鲨烯和氯化天竺葵素，对应作用靶标156个。其中与COVID-19的共同靶标112个，核心靶标38个。GO富集分析（P < 0.01）主要涉及脂多糖、细胞对缺氧的反应等。KEGG通路富集分析得到六堡茶干预COVID-19相关的HIF-1、IL-17、T细胞受体等信号通路。分子对接结果显示六堡茶中的6种主要化学成分可分别与受体蛋白M^pro结合较好，且结合能与现有报道推荐的临床使用化学药相近。六堡茶中的核心化学成分（+）-儿茶素、（-）-表没食子儿茶素没食子酸酯、α-菠甾醇、（-）-儿茶素没食子酸酯、角鲨烯、氯化天竺葵素与M^pro结合并通过MAPK1、TNF等炎症和免疫相关的靶标介导HIF-1、IL-17、T细胞受体等信号通路发挥干预COVID-19的功效。实验进一步对结合能较低的EGCG进行了M^pro的活力测定，发现IC₅₀为3.4 μmol/L，证实EGCG对M^pro有一定的抑制效果。
- 六堡茶 /
- COVID-19 /
- 网络药理学 /
- 分子对接 /
- SARS-CoV-2 3CL水解酶
Abstract: To investigate the material basis and mechanism of Liupao tea on preventing COVID-19 by network pharmacology and molecular docking.The active ingredients and targets of Liupao tea were searched through the literature and the TCMSP databases and the network between the two was built by Cytoscape 3.7.1.Then using GenCards platform to predict the disease targets,mapping the common targets between Liupao tea and disease.The common targets were imported into the STRING database for exploring the protein-protein interaction.Core targets were enriched by gene ontology (GO) enrichment analysis and KEGG (kyoto encyclopedia of genes and genomes) pathway enrichment analysis using DAVID database etc..Finally,the screened active components were docked with the receptor protein SARS-CoV-2 3CL hydrolase (M^pro).Six active ingredients of Liupao tea were screened,such as (-)-epigallocatechin gallate (EGCG),(+)-catechin,(-)-catechin gallate,α-spinasterol,pelargonidin chloride and squalene,and 156 targets were identified.Among them,there were 112 common targets and 38 core targets with COVID-19.GO enrichment analysis (P<0.01) involved lipopolysaccharide,cell response to hypoxia,etc..And the KEGG pathway enrichment analysis (P<0.01)was conducted to obtain the HIF-1,IL-17,T cell receptor and other signaling pathways associated with COVID-19.The results of molecular docking showed that the active ingredients of Liupao tea were well bound to the receptor protein M^pro.The active ingredients of Liupao tea may control HIF-1,IL-17,T cell receptors signaling pathways by binding M^pro hydrolase and acting on inflammation and immune related targets such as MAPK1,TNF to prevent COVID-19.The EGCG of M^pro activity was determined ,and the IC₅₀ was 3.4 μmol/L,which confirmed that EGCG was a certain inhibition effect on M^pro.
- Liupao tea /
- COVID-19 /
- network pharmacology /
- molecular docking /
- SARS-CoV-2 3CL hydrolase

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基于网络药理学和分子对接法研究六堡茶干预COVID-19的活性成分

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Potential active compounds of Liupao tea for prevention and treatment of COVID-19 based on network pharmacology and molecular docking

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