桑菊饮与德尔塔病毒——基于网络药理学与分子对接探究桑菊饮治疗德尔塔感染机制

Sangju Yin and Delta Variant—Potential Mechanism of Sangju Yin for the Treating Delta Variant Based on Network Pharmacology and Molecular Docking

摘要: 背景：桑菊饮在临床上通常用于治疗感冒、肺炎和其他类似疾病，也在治疗由德尔塔变体引起的新型冠状病毒感染中发挥了重要作用。目的：通过网络药理学和分子对接探索桑菊饮治疗德尔塔变体引起的新型冠状病毒感染的药理学机制。方法：在中药系统药理学数据库和分析平台(TCMSP)获取桑菊饮处方的有效成分和药物相关靶点，从GeneCards数据库获取德尔塔病毒相关靶点，利用CytoScape3.8.2软件和STRING数据库构建成分–靶点网络与蛋白–蛋白作用网络，通过基因本体论和京都基因百科全书呈现基因富集分析结果以及潜在信号通路。基于分子对接证实主要活性成分与病毒靶点存在相互作用。结果：最终收集到169种桑菊饮有效成分和6241个德尔塔病毒相关靶点，通过分析发现蛋白–蛋白作用网络的核心靶点JUN、MAPK3、STAT3和RELA与调节感染和转录通路关系紧密。GO和KEGG分析也揭示了PI3K-Akt、AGE-RAGE、cAMP、趋化因子和转录失调通路也许是桑菊饮治疗德尔塔病毒感染的核心通路。分子对接结果显示，桑菊饮核心活性成分与德尔塔病毒靶点ACE2、SARS-CoV-2 3CL具有良好的结合亲和力。结论：桑菊饮可通过多通路、多靶点控制德尔塔变体侵袭组织并控制细胞因子风暴的形成。

Abstract: Background: Sangju Yin (SJY) is often used to treat colds, pneumonia and other similar diseases in clinical, and also plays a key role in the treatment of severe coronavirus disease 2019 caused by the Delta variant. Objective: This study was purposed to explore the pharmacological mechanism of SJY treating the Delta variant through integrating network pharmacology and molecular docking. Methods: The effective ingredients and related targets of SJY were found in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database. The Delta-related targets were discerned from the GeneCards database. Compound-target and protein-protein interaction networks were estab-lished through CystoScape software 3.8.2 and STRING Software. Gene ontology and the Kyoto Ency-clopedia of Genes and Genomes were used to perform the enrichment of genes and potential signal pathways. Molecular docking was used to confirm the main active ingredients that interact with the viral hub targets. Results: 169 active compounds of SJY, and 6241 corresponding targets related to delta were collected. The analysis revealed that hub modules of the PPI network, including JUN, MAPK3, STAT3 and RELA, were closely associated with regulating inflammation and transcription pathways. And GO and KEGG analyses also revealed that PI3K-Akt, AGE-RAGE, cAMP, chemokine and transcriptional misregulation may be a central factor for Sangju Yin to treat COVID- 19. The re-sults of molecular docking showed that core active ingredients have good binding affinities with ACE2 and SARS-CoV-2 3CLpro. Conclusion: Sangju Yin could control the process of Delta variant in-vading tissues and the forming of cytokine storms through multiple channels and multiple targets.