用网络药理学和分子对接研究宣肺解热颗粒治疗COVID-19

Study on the effect of Xuanfei Jiere Granules in the treatment of COVID-19 by network pharmacology and molecular docking

目的 探寻宣肺解热颗粒治疗新型冠状病毒肺炎(Corona Virus Disease 2019,COVID-19)合并发热的作用机制。方法 用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)筛选宣肺解热颗粒的有效组分,并预测潜在靶基因,并用GeneCards和CTD数据库检索新型冠状病毒肺炎合并发热的相关疾病靶点,得到上述二者共有的靶点,导入Cytoscape中构建“成分-靶点-疾病”网络。将上述二者共有的靶点输入STRING蛋白相互作用在线数据库,将得到的数据结果导入Cytoscape软件获得PPI(protein-protein interaction)网络;用R语言对共同靶点进行GO(Gene Ontology)与KEGG(Kyoto Encyclopedia of Genes and Genomes)富集分析。结果 经筛选得到活性成分84个、靶点82个。通路富集分析显示,宣肺解热颗粒治疗新型冠状病毒肺炎合并发热主要作用于蛋白激酶B(Protein kinase B,AKT1)、肿瘤蛋白P53(Tumor Protein P53,TP53)和白细胞介素-6(Interleukin-6,IL-6)等关键靶点。KEGG通路富集分析显示,主要与影响流体剪切应力与动脉粥样硬化、人巨细胞病毒感染和糖尿病并发症中的AGE-RAGE等信号通路有关。分子对接结果显示,核心靶点与β-谷甾醇、刺芒柄花素及N-反式阿魏酰酪胺等有较强的的亲和力。结论 本研究初步验证宣肺解热颗粒可通过多成分、多靶点和多通路来发挥治疗COVID-19合并发热的作用。

Objective To explore the effect and mechanism of Xuanfei Jiere Granules in the treatment of corona virus disease 2019(COVID-19) complicated with fever.Methods The effective components of Xuanfei Jiere Granules were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the potential target genes were predicted. The disease targets of COVID-19 complicated with fever were searched by GeneCards and CTD databases, and the common targets were obtained, and then introduced into Cytoscape to construct the “component-target-disease” network. The above 2 common targets were input into the online database of STRING protein interaction, and the results were imported into Cytoscape software to obtain Protein-Protein Interaction(PPI) network;R language was used to analyze the common targets with Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis.Results 84 active components and 82 targets were obtained. The pathway enrichment analysis showed that Xuanfei Jiere Granules mainly acted on protein kinase B(AKT1), tumor protein P53(TP53), interleukin-6(IL6) and other key targets in the treatment of COVID-19 complicated with fever. KEGG pathway enrichment analysis showed that the action was mainly related to the influence of fluid shear stress and atherosclerosis, human cytomegalovirus infection, and AGE-RAGE in diabetic complications and other signal pathways. The results of molecular docking showed that the core target had strong affinity with β-sitosterol, formononetin, N-trans ferulyl tyramine and so on.Conclusion This study preliminarily verified that Xuanfei Jiere Granules can play a role in the treatment of COVID-19 complicated with fever through multi-components, multi-targets and multi-pathways.