摘要
目的:运用网络药理学与分子对接方法预测黄酮类化合物治疗新型冠状病毒肺炎(COVID-19)的作用机制,以揭示中药有效成分在治疗COVID-19中的作用机理。方法:通过TCMSP数据库,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18为阈值筛选潜在的黄酮化合物,建立黄酮类化合物基本药物参数,收集其疾病作用靶点;通过GeneCards数据库和Uniprot数据库,运用perl脚本文件,利用Cytoscape3.7.2软件制作化合物-全靶点图和化合物-COVID-19靶点图;利用STRING数据库获取蛋白-蛋白相互作用(PPI)网络;通过Metascope数据库进行基因本体(GO)功能富集分析,利用R语言和Bioconductor程序运算得KEGG通路富集分析,并预测其作用机制。利用AutoDock将黄酮类化合物与新型冠状病毒(SARS-CoV-2)S蛋白受体结合结构域匹配的血管紧张素转化酶II(ACE2)蛋白酶进行分子对接并计算结合能。结果:筛选得到黄酮类化合物18个,共作用于疾病靶点264个,得到COVID-19疾病靶点350个,二者共同作用的交集靶点55个。GO功能富集分析发现,黄酮类化合物涉及多种免疫学抗炎机制,主要对细胞因子介导的信号转导、趋化因子、磷酸化和线粒体凋亡等生物学过程起重要调节作用。通过KEGG通路富集分析,共富集通路155条,发现黄酮类化合物可以调控病毒炎症通路及呼吸道感染通路。分子对接及结合能计算显示黄酮类化合物与ACE2结合能小,分子对接效果十分优秀,其中异鼠李素、黄芩素可能作为抗SARS-CoV-2的潜在活性成分,其作用机制可能是通过影响新型冠状病毒S蛋白受体结构域与ACE2蛋白结构域复合物结构的稳定从而起到抗病毒的作用。结论:黄酮类化合物具有多靶点、多通路、多系统调节疾病的特点,并可通过其特点对COVID-19提供潜在的治疗价值,为临床救治与合理用药提供理论依据。
Objective:Prediction of the mechanism of flavonoids in the treatment of COVID-19 by network pharmacology and molecular docking so as to reveal the mechanism of the effective components of traditional Chinese medicine in the treatment of COVID-19.Methods:The potential flavonoids were screened by TCMSP database with the threshold of oral bioavailability(OB)≥30%and drug-like(DL)≥0.18.Through the GeneCards database and the Uniprot database,compound full target map and compound-COVID-19 target map were made using perl script files in Cytoscape3.7.2 software.The protein-protein interaction(PPI)network was obtained by STRING database.Metascope database was used to carry out functional enrichment analysis of gene ontology(GO),and KEGG pathway enrichment analysis was obtained by using R language and Bioconductor program,and its mechanism of action was predicted.Flavonoids were docked into angiotensin-converting enzyme II(ACE2)protease,which matches the novel coronavirus S protein receptor binding domain,by AutoDock and the binding energy was calculated.Results:Eighteen flavonoids were identified,which were recognized by 264 disease targets.Additionally,350 disease targets of COVID-19 were obtained,and 50 common targets were found.GO functional enrichment analysis revealed that flavonoids were involved in a variety of immunological anti-inflammatory mechanisms and play an important regulatory role in biological processes,such as cytokine mediated signal transduction,chemokines,phosphorylation and mitochondrial apoptosis.The enrichment of 155 pathways by KEGG pathway showed that flavonoids could regulate viral inflammatory pathways and respiratory tract infection pathways.Molecular docking and binding energy calculation showed that the binding energy of flavonoids and ACE2 was low,indicating that the interaction is strong.Isorhamnetin and baicalein might be potential active components of anti-SARS-CoV-2 by stabilizing the complex structure of the S receptor domain and ACE2 protein domain.Conclusion:flavonoids have the characteristics of multi-target,multi-pathway and multi-system to regulate diseases,and can provide potential therapeutic value for COVID-19 through its characteristics.Our results provide theoretical basis for clinical treatment and rational drug use.
作者
曲一帆
徐凤英
王玉珍
谢基明
QU Yifan;XU Fengying;WANG Yuzhen;XIE Jiming(Graduate College,Inner Mongolia Medcial University,Hohhot 010060,China;Department of Pharmaceutical Engineering,Inner Mongolia Argicultural University;Clinical Laboratory,Inner Mongolia People's Hospital)
出处
《包头医学院学报》
CAS
2020年第3期74-78,86,共6页
Journal of Baotou Medical College
作者简介
通讯作者:谢基明
