基于网络药理学与分子对接技术的荆银合剂干预新型冠状病毒肺炎的作用机制研究

目的 应用网络药理学和分子对接的方法 ,探讨荆银合剂干预新型冠状病毒肺炎(COVID-19)的分子靶点及可能机制.方法 ? 利用中药系统药理学数据库和分析平台(TCMSP)检索荆银合剂的潜在入血活性成分和靶点.通过GeneCard数据库检索COVID-19相关靶点.利用STRING 10.5软件构建荆银合剂成分靶点与COVID-19靶点的蛋白质-蛋白质相互作用(PPI)网络.利用R 3.6软件进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)富集分析;采用AutoDock Tools 1.5.6和AutoDock Vina 1.1.2软件进行分子对接研究.结果 根据药动学参数口服生物利用度和类药性筛选出120种活性成分,并获得了与这些成分相关的232个靶点.从GeneCard数据库中获得350个与COVID-19直接相关的靶点,从成分靶点与疾病靶点网络的交集中获得47个靶点,这些靶点主要参与细胞内脂多糖反应、氧化应激反应、对机械刺激的反应等生物学过程.分子功能主要包括细胞因子受体结合、细胞因子活性、受体配体活性等,其机制与低氧诱导因子1信号通路、NF-κB信号通路、细胞凋亡等有关.分子对接结果 显示荆银合剂中槲皮素、木樨草素与6LU7和6M3M蛋白具有一定的亲和力.结论 荆银合剂的活性成分可能通过抗病毒、抗炎、调控细胞周期对COVID-19及其导致的炎症和肺损伤具有潜在的干预作用,研究结果 可为中医药干预COVID-19提供一定的理论基础与科学依据.

Effect of Jingyin mixture on coronavirus disease 2019: a molecular mechanism study based on network pharmacology and molecular docking

Objective To explore the molecular targets and mechanism of Jingyin mixture for the treatment of coronavirus disease 2019 (COVID-19) by using network pharmacology and molecular docking. Methods The potential active components in the plasma and targets of Jingyin mixture were retrieved using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). COVID-19-related gene targets were retrieved from GeneCard database. The protein-protein interaction (PPI) network between Jingyin mixture component-targets and COVID-19 targets was constructed by STRING 10.5. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted by R 3.6 software. AutoDock Tools 1.5.6 and AutoDock Vina 1.1.2 were used for molecular docking. Results A total of 120 active components were identified according to the pharmacokinetic parameters (oral bioavailability and drug likeness), and 232 targets related to these constituents were obtained. Altogether 350 target genes directly related to COVID-19 were obtained from GeneCard database, and 47 genes were obtained from the intersection of component-target and disease-target. These genes were mainly involved in the responses to intracellular lipopolysaccharide, oxidative stress, mechanical stimulation, and other biological processes. Molecular functions were mainly related to cytokine receptor binding, cytokine activity, receptor ligand activity, etc, with their mechanisms related to hypoxia-inducible factor 1 signaling pathway, nuclear factor κB (NF-κB) signaling pathway, apoptosis, etc. The results of molecular docking showed that quercetin and luteolin in Jingyin mixture had certain affinity with 6LU7 and 6M3M protein. Conclusion The active components of Jingyin mixture may have potential intervention effect on the inflammation and lung injury caused by COVID-19 through antiviral, anti-inflammatory effects and regulation of cell cycle. The results of this study provide theoretical and scientific evidence for the intervention of COVID-19 by traditional Chinese medicine.