基于网络药理学和分子对接技术探讨柴银颗粒抗冠状病毒感染潜在分子机制

Potential molecular mechanism for Chaiyin Granules against coronavirus infection based on network pharmacology and molecular docking

目的基于网络药理学和分子对接分析柴银颗粒抗冠状病毒感染的分子机制。方法从TCMSP数据库中获取柴银颗粒成分,其潜在靶点以及冠状病毒作用靶点分别利用SwissTargetPrediction数据库和GeneCards数据库获取。通过绘制韦恩图发现柴银颗粒抗冠状病毒感染的潜在药效成分和作用靶点。潜在药效成分-作用靶点网络和潜在作用靶点的互作网络可视化由Cytoscape 3.7.0软件完成。GO功能和KEGG通路分析在String数据库中进行。潜在药效成分和关键靶点的分子对接由autodock vina 1.1.2实现。结果发现了柴银颗粒抗冠状病毒感染的51个潜在药效成分和14个潜在作用靶点。生物信息学分析发现PI3K-Akt、IL-17等信号通路与柴银颗粒抗冠状病毒感染的分子机制相关。分子对接结果显示柴银颗粒中的黄芩苷等成分与NTRK2等靶点的亲和力强。结论柴银颗粒中的黄芩苷、荜澄茄素、黄连碱等作用于NTRK2、PRKCα、TNF等,调节PI3K-Akt/m TOR、Erb B/Ras和IL-17等信号通路抑制冠状病毒的侵袭和复制,增强宿主免疫能力,实现抗冠状病毒感染。

Objective To reveal the molecular mechanism of Chaiyin Granules in treatment of coronavirus infection based on network pharmacology and molecular docking. Methods The chemical constituents of Chaiyin Granules were collected by TCMSP database. SwissTargetPrediction database and GeneCards database were used to predict the potential targets of active ingredients and coronavirus. The potential active ingredients and its targets of Chaiyin Granules in the treatment of coronavirus infection were found through Venn diagram. The potential active compounds-targets network and the PPI network were visualized by Cytoscape 3.7.0. GO-enriched analysis and KEGG pathways analysis were constructed on STRING database. The molecular docking of potential active compounds and key targets was achieved by autodock vina 1.1.2. Results Fifty-one potential active ingredients and 14 potential targets for Chaiyin Granules on treatment of coronavirus infection were obtained. KEGG pathways analysis showed that 44 metabolic pathways were involved to Chaiyin Granules effect on coronavirus infection, including MAPK signaling pathway, PI3 K-Akt signaling pathway, mTOR signaling pathway, Fc epsilon RI signaling pathway and IL-17 signaling pathway. The results of molecular docking showed that baicalin, cubebin, coptisine, daidzein-4,7-diglucoside, linarin, liquiritin, luteolin and wogonin in Chaiyin Granules had strong affinity with NTRK2, PRKCα, TNF, VEGFA, GSK3β. Conclusion This study elaborated that baicalin, cubebin and coptisine in Chaiyin Granules interacted with NTRK2, PRKCα, TNF, VEGFA, GSK3β and regulated PI3 K-Akt/mTOR, ErbB/Ras and IL-17 signaling pathways to inhibit the invasion and replication of coronavirus and enhance immunity to battle against coronavirus infection. This study provides a research basis and theoretical basis for the application of Chaiyin Granules in the treatment of anti-coronavirus infection.