基于网络药理学的牡丹属抗流感病毒的作用机制研究

Exploration on mechanism of anti-influenza virus activity of genus Paeonia based on network pharmacology

该研究采用网络药理学虚拟筛选的方法,筛选牡丹抗流感病毒作用的潜在活性成分,预测抗流感病毒的作用靶点,探讨牡丹抗流感病毒活性的作用机制。首先,通过近10年中外文文献的查询汇总了牡丹属301个小分子化合物,使用PubChem和Chemical Book等数据库进行结构确认,并借助Chem Draw,Avogadro和Discovery Studio Visualizer软件对其进行分子对接配体的构建。其次,结合STITCH靶标数据库和文献的查找拟定了23个潜在抗流感病毒的作用靶点,采用Uniprot数据库找到相对应的基因靶点,并通过RCSB网站寻找相对应的蛋白亚型的PDB ID以及阳性小分子结构为分子对接的受体,利用Quick Vina 2.0软件进行分子对接。最后,借助Cytoscape 3.5.1软件绘制牡丹抗流感病毒潜在活性成分与抗流感病毒作用靶点网络图,使用Uniprot在线数据库进行其靶点GO分析和KEGG代谢通路分析。结果显示,牡丹中有74个化合物具有良好抗流感病毒作用,筛选得到18个潜在的抗流感病毒作用靶点,通过GO分析推断牡丹抗流感病毒的作用机制与神经氨酸酶抗流感病毒机制基本一致,以阻止病毒的出芽、分散、扩散,使病毒的感染能力下降,使感染受限,从而达到抗流感病毒的作用。

This paper aimed to investigate the anti-influenza virus activity of the genus Paeonia,screen potential anti-influenza virus compounds and predict targets of anti-influenza virus to explore the mechanism of anti-influenza virus activity. First of all,a total of301 compounds of the genus Paeonia were summarized from the literatures in recent ten years. The candidate active ingredients from the genus Paeonia were identified by database such as Pub Chem and Chemical Book. The ligands were constructed by Chem Draw,Avogadro and Discovery Studio Visualizer. Secondly,23 potential anti-influenza virus targets were developed by combining the target database and the literatures. Uniprot database was used to find the anti-influenza virus targets,and RCSB was used to identify targets associated with anti-influenza virus activity as docked receptor proteins. Quick Vina 2. 0 software was used for molecular docking. Finally,the Cytoscape 3. 5. 1 software was used to map the potential activity compounds of the genus Paeonia against influenza virus and the anti-influenza virus target network. Uniprot online database was used to analyze the target GO enrichment and KEGG metabolic pathways. The results showed that 74 compounds of the genus Paeonia had anti-influenza virus effect and 18 potential anti-influenza virus targets were screened. GO analysis concluded that the mechanism of the genus Paeonia anti-influenza virus is consistent with the mechanism of NA anti-influenza virus in order to stop the sprouting,dispersion and diffusion of virus and reduce the ability of virus to infect,so that the infection can be restricted so as to achieve the anti-influenza virus effect.