从病毒-宿主交互界面探讨加味芦根方（芦根、全蝉蜕、僵蚕、金银花、生甘草、薄荷、羌活、 葛根、柴胡）治疗流行性感冒的分子机制。方法从本草组鉴数据库收集复方的化学成分，经里宾斯基五原则 筛选潜在的活性成分后，进一步在瑞士靶点预测网站预测活性成分的作用靶点；从GEO 数据库挖掘人类流感 芯片GSE90732 的差异表达基因；从病毒-宿主相互作用搜索工具检索H1N1 流感-智人蛋白交互组；整合上述 生物信息集，通过Cytoscape 构建蛋白质-蛋白质相互作用网络和加味芦根方-病毒-宿主交互网络，使用R 软件对交集基因进行功能富集分析，最后对关键活性成分及靶点进行分子对接验证。结果获得1 252 个活性 成分，1 415 个作用靶点，951 个流感差异表达基因和10 142 对H1N1-智人蛋白互作信息。加味芦根方与流感 的交集靶点有72 个，功能富集显示这些靶点与宿主防御和程序性细胞死亡密切相关。交互网络拓扑分析表明， 加味芦根方通过齐墩果酸、γ-十一碳酸内酯、长棘素等多种活性成分调控病毒M2、NA、NS1 和HA 蛋白和/ 或宿主HSP90AA1、NRAS 和ITGB1 等多个关键靶标发挥治疗作用，分子对接结果表明活性成分与靶点具有较 好的结合能力。结论加味芦根方通过多种活性成分直接靶向流感病毒蛋白和/或宿主因子，从抑制病毒复制、 调节宿主防御和细胞死亡等多个维度发挥抗击流感的作用。该研究为进一步实验解析加味芦根方治疗流感的分 子机制提供了理论基础。

To explore the therapeutic mechanism of Modified Lugen Formula （Phragmitis Rhizoma，Cicadae Periostracum，Batryticatus Bombyx，Lonicerae Japonicae Flos，Glycyrrhiza，Menthae Haplocalycis Herba， Notopterygii Rhizoma et Radix， Puerariae Lobatae Radix， Bupleuri Radix） in treating influenza from the virushost interaction interface. Methods The phytocompounds were first collected from the HERB database， and then potential active compounds were screened out by Lipinski's rules of five. The targets of active compounds were further predicted through the SwissTargetPrediction platform. Differentially expressed genes（DEGs）were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database（GEO）. H1N1-Homo sapiens-related protein-protein interactions（PPIs）were gathered from the Pathogen-Host Interaction Search Tool （PHISTO） . The above mentioned bioinformatic datasets were integrated. Then a PPI network and a Formula - virus-host interaction network were constructed using Cytoscape. Functional enrichment analyses were performed by using R software. Finally，molecular docking was carried out to evaluate the binding activities between the key compounds and targets. Results A total of 1 252 active compounds，1 415 targets，951 influenza-related DEGs， and 10 142 H1N1-Homo sapiens-related PPIs were obtained. There were 72 intersection targets between the Modified Lugen Formula and influenza. Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death. The network topological analysis showed that active compounds in the Modified Lugen Formula， such as oleanolic acid， γ - undecalactone， and longispinogenin， regulate viral proteins M2，NA，NS1，and HA and/or the host factors HSP90AA1，NRAS，and ITGB1，thus exert therapeutic effect. Molecular docking results confirmed that these compounds had a good binding ability with the targets. Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors， thereby play an anti-influenza role in multiple dimensions， including inhibiting virus replication， regulating host defense and cell death. This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

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国家自然科学基金项目（82274418，81973814）；广东省中医药管理局项目（20231093）；广东省重点领域研发计划项目（2020B1111100002）； COVID-19治疗与预防技术研究及中医药应用专项——中医药防治病毒性传染病平台建设研究（2020KJCX-KTYJ-130）；深圳市科学技术和创新 委员会项目（JSGG20220226090550002， JCYJ20190808160407500）； 深圳市“ 医疗卫生三名工程”建设项目（SZZYSM202206013； SZZYSM202106006）；广州中医药大学“双一流”和高水平大学学科协同创新团队项目（2021XK16）；广东省普通高校重点领域专项项目 （2022ZDZX2014）。