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中国医药导刊 ›› 2021, Vol. 23 ›› Issue (2): 109-119.

• 基础研究 • 上一篇    下一篇

基于网络药理学与分子对接方法的苓甘五味姜辛汤抗新冠肺炎(COVID-19)的作用机制与活性成分研究

  杨晶晶1, 曹灿2, 崔瑛2,3, 史银玥2, 楚玉玺2, 巫晓慧2   

  1. 1. 河南省中医药研究院附属医院, 河南 郑州 450000;
    2. 河南中医药大学, 河南 郑州 450046;
    3. 河南中医药大学 呼吸疾病中医药防治省部共建协同创新中心, 河南 郑州 450000
  • 收稿日期:2020-12-25 修回日期:2021-01-07 出版日期:2021-02-28 发布日期:2021-03-31
  • 基金资助:
    国家自然科学基金项目(项目编号:81473368;项目名称:基于“病证-效应-生物样本分析”方法的生姜、干姜、炮姜药性物质研究)

Mechanism and Active Components of Linggan Wuwei Jiangxin Decoction in the Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking

  1. 1. The Affiliated Hospital of Henan Academy of Chiese Medicine, Henan Zhengzhou 450000, China
    2. Henan University of Chinese Medicine, Henan Zhengzhou 450046, China;
    3. Henan University of Chinese Medicine/Collaborative Innovation Center for Chinese Medicine and Respiratory Disease
         Co-Constructed by Henan Province and Education Ministry of P.R.China, Henan Zhengzhou 450000, China
  • Received:2020-12-25 Revised:2021-01-07 Online:2021-02-28 Published:2021-03-31

摘要: 目的:采用网络药理学与分子对接法研究苓甘五味姜辛汤抗新冠肺炎(COVID-19)的作用机制与活性成分。方法:借助TCMSP数据库检索苓甘五味姜辛汤的化学成分及成分作用靶点,通过Swiss Target Prediction数据库剔除可能性为0的靶点。以“coronavirus” “pneumonia” “cough” “fever”为检索词在GeneCards及OMIM数据库中检索疾病相应靶点。通过Uniprot数据库校正药物和疾病靶点名称,取苓甘五味姜辛汤与疾病靶点交集,进而运用Cytoscape 3.7.2软件构建中药-化合物-靶点网络进行可视化,用靶点交集通过STRING数据库构建蛋白互作(PPI)网络,DAVID数据库进行GO功能富集分析和KEGG通路富集分析,预测交集靶点作用机制,并进行可视化。将中药-化合物-靶点网络中的化合物与新型冠状病毒(SARS-CoV-2)3CL水解酶和血管紧张素转化酶II(ACE2)进行对接,选取与SARS-CoV-2 3CL水解酶结合能最小的6个化合物作为核心活性成分,做进一步研究。结果:中药-化合物-靶点网络包含了5种中药,67个化合物和靶点141个。PPI网络的关键基因涉及AKT1、MAPK1、MAPK3等,GO功能富集分析得到条目104个,KEGG通路富集分析筛选得到99条信号通路。分子对接结果显示6个核心活性成分甘草异黄烷酮、卡里宾、甘草素L、夏姆比奥纳、光甘草宁、五味子素R,与SARS-CoV-2 3CL水解酶及ACE2的结合能普遍较推荐化药小。结论:苓甘五味姜辛汤中的化合物能通过与SARS-CoV-2 3CL水解酶和ACE2结合作用于AKT1、MAPK1、MAPK3等靶点,调节朊病毒病信号通路、非洲淋巴细胞瘤病毒感染通路、小细胞肺癌信号通路和非小细胞肺癌信号通路等发挥抗COVID-19作用。
     

关键词: font-size:medium, ">网络药理学;苓甘五味姜辛汤;新冠肺炎;分子对接;SARS-CoV-2 3CL水解酶;ACE2

Abstract: Objective: To investigate treatment mechanism and active ingredients of linggan wuwei jiangxin decoction in the treatment of the novel coronavirus pneumonia (COVID-19) by network pharmacology and molecular docking. Methods:TCMSP database was used to search the chemical composition and target of linggan wuwei jiangxin decoction, and Swiss Target Prediction database was used to remove the target with 0 possibility. Using "coronavirus" "pneumonia" "cough" and "fever" as search words, the corresponding disease targets were searched in GeneCards and OMIM database. The names of drugs and disease targets were corrected by UniProt database, and the intersection of linggan wuwei jiangxin decoction and disease targets was selected, and then the software Cytoscape 3.7.2 was used to constructs the Chinese herbal medicine-compound-target network for visualization. Target intersection was used to construct the protein interaction (PPI) network through the STRING database, and on the GO function enrichment analysis and the KEGG pathway enrichment analysis were carried on through the DAVID database to forecast the mechanism of the interaction target, and carries on the visualization. The SARS-CoV-2 3CL hydrolase and angiotensin-converting enzyme Ⅱ(ACE2) were co-located with the compounds in the Chinese herbal medicine compound-target network, and the 6 compounds with the smallest binding energy of SARS-CoV-2 3CL hydrolase were selected as the core active components for further study. Results:The TCM compound target network contains 5 kinds of TCM, 67 compounds and 141 targets. The key genes of PPI network include AKT1, MAPK1, MAPK3, etc. 104 entries were obtained by GO function enrichment analysis, and 99 signal pathways were obtained by KEGG pathway enrichment analysis. The results of molecular docking showed that the binding energy of six core active components, Isoflavanone, Caribin, Glycyrrhizin L, Xambioona, Glabranin, Gomisin R, whose binding energy with SARS-CoV-2 3CL hydrolase and ACE2 were generally smaller than that of the recommended drugs. Conclusion: The compounds in linggan wuwei jiangxin decoction can play an anti COVID-19 role by binding with SARS-CoV-2 3CL hydrolase and ACE2 to target AKT1, MAPK1, MAPK3 by Prion diseases signal pathway, Epstein-Barr virus infection pathway, small cell cancer signal pathway and non-small cell lung cancer signal pathway.
 

Key words: font-size:medium, ">Network pharmacology; Linggan Wuwei Jiangxin Decoction; COVID-19; Molecular docking; SARS-CoV-2 3CL hydrolase; ACE2

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