基于虚拟筛选技术的清感冬饮防治新型冠状病毒感染的潜在活性成分与作用机制研究

Study on potential active compounds and mechanism of Qinggandong Decoction for the prevention and treatment of COVID-19 via virtual screening technology

关键词:  清感冬饮  网络药理学  分子对接  COVID-19

Key words:  Qinggandong Decoction  network pharmacology  molecular docking  COVID-19

摘要:

[目的] 通过网络药理学及分子对接等虚拟筛选技术探究清感冬饮(QGDD)防治新型冠状病毒肺炎(COVID-19)的潜在活性成分及作用机制,为清感冬饮的临床应用提供科学依据。[方法] 基于清感冬饮已鉴定的化学成分,以GeneCards和DrugBank数据库检索靶标信息,通过Origin、STRING 和Cytoscape构建"药材-制剂-成分-靶点""蛋白-蛋白相互作用""药材-归经"等网络,采用 DAVID进行功能富集分析。采用BIOVIA Discovery Studio 2020进行潜在活性成分和关键靶点的分子对接。[结果] 清感冬饮的11味中药中有9味归肺经,筛选获得的45个潜在活性成分与COVID-19的共有靶点66个,GO功能富集分析得到324个生物过程条目、24个细胞组分条目、45个分子功能条目,KEGG富集分析得到123条信号通路,与免疫调节、抗病毒感染和炎症损伤修复相关。分子对接显示组方中多个化合物与主要靶点受体TNF-α、AKT1、VEGFA和ACE2具有中等强度以上的潜在相互作用,提示组方通过多组分配伍,协同发挥防治COVID-19的功效,金银花和红茶中的山柰酚-3-O-芸香糖苷和芦丁等黄酮类化合物与靶点的对接强度最高,是潜在的活性成分。[结论] 研究初步揭示了清感冬饮防治新冠肺炎的潜在物质基础与作用机制,清感冬饮可能通过山柰酚-3-O-芸香糖苷、芦丁等主要黄酮类成分作用于TNF-α、AKT1、VEGFA和ACE2等靶点,通过参与脂质代谢与动脉粥样硬化、Toll样受体信号通路、IL-17信号通路等发挥抗炎、抗病毒的作用,为深入研究清感冬饮防治新冠肺炎提供了科学理论支持。

Abstract:

[Objective] The study aimed to explore the potential active compounds and mechanism of Qinggandong decoction (QGDD) for its prevention and treatment of novel coronavirus disease 2019 (COVID-19) via network pharmacology and molecular docking,and provide evidence for clinical applications of QGDD.[Methods] These compounds were identified by LC-MS/MS from QGDD in previous study,and the disease targets were collected by databases of GeneCards and DrugBank. The networks of herb-preparation-ingredient-target,protein-protein interaction (PPI),and herb-meridian tropism were constructed by Origin,STRING and Cytoscape. GO and KEGG enrichment analysis were carried out by DAVID. The potential active compounds were docked with the key targets by BIOVIA Discovery Studio 2020.[Results] Nine of the 11 herbs in QGDD belonged to the lung meridian,and there were 66 common targets for the 45 potential active compound targets and COVID-19 targets. GO functional enrichment analysis obtained 324 biological process items,24 cellular component items and 45 molecular functional items. KEGG enrichment analysis obtained 123 pathways,which were related to immune regulation,viral infection and inflammatory damage repair. The docking results showed that multiple compounds had potential interactions above medium intensity with the main targets,including TNF-α,AKT1,VEGFA and ACE2,suggesting that the formula may prevent and treat COVID-19 through multicomponent combination. Kaempferol-3-O-rutinoside and rutin,as the major compounds of the flavonoid group,shows the highest docking intensity with the targets.[Conclusion] This study preliminarily reveals the potential active compounds and therapeutic mechanism of QGDD for prevention and treatment of COVID-19. The active compounds from QGDD,such as kaempferol-3-O-rutinoside and rutin,may act on the targets as TNF-α,AKT1,VEGFA and ACE2,which play an anti-inflammatory and antiviral role by participating in lipid and atherosclerosis,chagas disease,Toll-like receptor signaling pathway,IL-17 signaling pathway,and so on. Our study will provide the scientific evidence for the further study on COVID-19 of QGDD.