基于网络药理学和分子对接技术预测催汤颗粒治疗新型冠状病毒肺炎(COVID-19)的物质基础与作用机制研究
Prediction of the material basis and mechanism of Cuitang granules for the treatment of novel coronavirus pneumonia (COVID-19) using pharmacoinformatics and molecular docking techniques
投稿时间:2020-07-19  修订日期:2020-09-08
DOI:
中文关键词: 催汤颗粒  新冠状病毒(SARS-CoV-2)  新型冠状病毒肺炎(COVID-19)  网络药理学  分子对接
英文关键词: Cuitang granules  SARS-CoV-2  COVID-19  Pharmacoinformatics  Molecular docking
基金项目:十三五科技部重大新药创制子项目(2017BA20060007)
作者单位E-mail
陈旅翼 中南民族大 clyhappy05@163.com 
刘鹏 中南民族大  
王静 中南民族大  
刘新桥 中南民族大  
陆少娟 中南民族大  
陈维武 西藏奇正藏药股份有限公司  
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中文摘要:
      目的 采用网络药理学与分子对接法,初步探索催汤颗粒治疗新型冠状病毒肺炎(COVID-19)的物质基础和可能机制。方法 借助TCMSP和化学专业数据库检索催汤颗粒,构建化学成分数据库并在PubChem获取化合物分子结构式,输入SWISS数据库获得成分预测靶点。通过GeneCards数据库获取冠状病毒靶点,运用Venny2.1.0在线作图工具平台获取催汤颗粒和冠状病毒的交叉靶点;将交叉靶点输入Cytoscape软件,绘制药物-成分-靶点-疾病网络图;利用STRING 数据库获取化合物靶点相互作用(PPI)图,通过Enrichr网络平台对核心靶点开展GO富集分析和KEGG通路分析;运用分子对接技术虚拟筛选与SARS-CoV-2 3CL水解酶以及血管紧张素转换酶II(ACE2)结合力较强的活性成分,预测可能的结合位点。结果 经数据库分析,筛选获得催汤颗粒120个化合物,涉及479个核心靶点,与冠状病毒疾病靶点(351个)交叉60个,涉及IL-6,TNF,MAPK1,MAPK3,EGFR,MAPK8,CASP3等。GO功能富集分析结果显示催汤颗粒主要对细胞表面信号转导、分子功能、磷酸化和转录等生物学过程起调节作用,KEGG通路富集主要涉及缺氧诱导因子1信号通路、病毒感染通路、TNF信号通路、VEGF信号通路和凋亡相关通路等。分子对接结果显示催汤颗粒中多个核心成分与SARS-CoV-2 3CL水解酶及ACE2的亲和作用较好。结论 催汤颗粒具有多成分,多靶点,多途径的整体调控COVID-19相关靶标,从而发挥临床作用。
英文摘要:
      Objective Preliminary exploration of the material basis and possible mechanisms of Cuitang granules for the treatment of novel coronavirus pneumonitis (COVID-19) with catalytic soup particles using pharmacoinformatics and molecular docking. METHODS The TCMSP and chemistry specialty databases were used to Cuitang granules, construct a chemical composition database and obtain the molecular structure formula of the compound in PubChem, and enter the composition prediction targets into the SWISS database. The GeneCards database was used to obtain coronavirus targets, and the Venny2.1.0 online mapping tool platform was used to obtain cross-targets of Cuitang granules and coronavirus; the cross-targets were entered into Cytoscape software to draw drug-component-target-disease network maps; the STRING database was used to obtain compound-target interaction (PPI) maps, and the Enrichr network platform was used to perform GO enrichment analysis and KEGG pathway analysis on core targets; the molecular docking technique was used to virtually screen active components that bind strongly to SARS-CoV-2 3CL hydrolase and key receptor angiotensin-converting enzyme II (ACE2) in SARS-CoV-2-infected target cells to predict possible binding sites. Results Obtaining 120 compounds from Cuitang granules by screening involving 479 core targets, 60 crossed with coronavirus disease targets (351), involving IL-6, TNF, MAPK1, MAPK3, EGFR, MAPK8, CASP3, etc. GO functional enrichment analysis showed that Cuitang granules mainly regulate the biological processes of cell surface signal transduction, molecular function, phosphorylation and transcription, and the KEGG pathway enrichment mainly involves the hypoxia-inducible factor 1 signaling pathway, viral infection pathway, TNF signaling pathway, VEGF signaling pathway and apoptosis-related pathway. Molecular docking results show that Phyllanthin、Acanthoside B and other key compounds have a certain degree of affinity with SARS-CoV-2 3CL hydrolase and ACE2. Conclusion Cuitang granules has a multi-component, multi-target, multi-pathway integrated modulation of COVID-19-related targets to achieve clinical efficacy.
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