基于网络药理学的黄酮类化合物抗流感病毒作用机制研究

Study on the Mechanism of Flavonoid Anti-Influenza Virus Action Based on Network Pharmacology

摘要: 通过利用网络药理学的方法寻找黄酮类化合物与人类流感病毒结合能力较好的活性成分，研究其预防治疗流感病毒的可能性。利用TCMSP和GeneCards、TTD等数据库获取黄酮类化合物抗流感病毒的靶点，利用在线分析平台STRING对靶蛋白之间相互作用进行研究，采用Cytoscape软件绘制靶点–靶点网络图，然后使用DAVID平台GO和KEGG程序对核心靶点的功能和参与调控通路进行分析，并绘制靶点–通路网络节点图，最后使用Autodock软件将可能有效的化合物与流感病毒相关分子进行分子对接，计算它们的结合能并判断是否有效结合。最终获得橘皮苷靶点6个，黄芩素靶点37个，二氢杨梅素靶点7个，流感靶点10,448个，新冠肺炎靶点7566个，在橘皮苷–流感中，发现CASP3靶点通过“AGE-RAGE”信号通路来作用于人体；在黄芩素–流感中，发现AKT1靶点通过信号通路中节点度值最高的“癌症的途径”信号通路作用于人体；在二氢杨梅素–流感中，发现VEGFA靶点通过“卡波西肉瘤相关疱疹病毒感染”信号通路作用于人体。本研究初步发现了黄芩素在三个药物中与流感的RIG-I和新冠肺炎的ACE2分子具有最好的结合效能，最有预防治疗疾病的可能性。

Abstract: To explore the possibility of preventing and treating influenza viruses by using network pharmacological methods to search for active components of flavonoid that can bind well with human influenza viruses. The databases such as TCMSP, GeneCards and TTD were used to identify flavonoid targets. The on-line analysis platform STRING was used to study the interaction between target proteins, and the Cytoscape software was used to draw the target-target network. Then, the function and participating regulatory pathways of the core targets were analyzed by using DAVID Platform GO and KEGG program, and the node diagram of the target-pathway network was drawn. Finally, the possible effective compounds were docked with influenza virus-related molecules by Autodock software, and the binding energy was calculated to judge whether the effective binding was or not. Finally, 6 Hesperidin targets, 37 Baicalein targets, 7 Dihydromyricetin targets, 10,448 influenza targets and 7566 COVID-19 targets were obtained. In hesperidin-influenza, CASP3 targets are most likely to act through the “AGE-RAGE” signaling pathway. In baicalein-influenza, the “cancer pathway” signaling pathway has the highest degree of node degree in the signaling pathway. In dihydromyricetin-influenza, the VEGFA target was most likely to act through the Kaposi’s sarcoma-associated herpesvirus infection signaling pathway. In this study, Baicalein was found to have the best binding activity with RIG-I of influenza and ACE2 of COVID-19 among the three drugs, and had the best possibility to prevent and treat the disease.