基于“药物-靶点-通路”网络的血必净注射液治疗COVID-19作用机制研究

The Mechanism of Xuebijing Injection in the Treatment of COVID-19 Based on the “Drug-target-pathway” Network

目的:采用网络药理学方法分析血必净注射液活性成分通过调节免疫与炎症反应治疗新型冠状病毒肺炎(COVID-19)的作用机制,为其临床运用提供理论依据。方法:通过检索文献获取血必净注射液体内活性成分,采用TCMSP、DrugBank数据库筛选活性成分及预测对应的作用靶点。在TTD、DisGeNT数据库搜索COVID-19相关的免疫与抗炎靶点,与血必净注射液靶点映射筛选出共同靶点,采用Cytoscape 3.5.1软件构建中药-成分-靶点网络图;将共同靶点导入STRING数据库中构建蛋白质-蛋白质相互作用网络图。结合网络图筛选出血必净注射液的核心靶点。通过DAVID数据库进行GO生物学过程和KEGG信号通路富集分析。采用Auto Dock4.2对血必净注射液核心成分与SARS-CoV-23CL水解酶蛋白进行分子对接。结果:血必净注射液共有116种活性成分,其中关键成分29个。COVID-19相关的免疫与抗炎靶点541个,血必净注射液与COVID-19交集有75个靶点,其中关键蛋白靶点55个,关键活性成分4个,864条相互作用关系。GO条目93个。KEGG通路分析关键靶点与炎症免疫反应相关27条。分子对接结果显示,紫丹参素C、鼠尾草酚酮、β-谷甾醇、丹参新醌D、槲皮素、山柰酚、木犀草素、黄芩素等活性成分与SARS-CoV-23CL有较强的结合能力。结论:血必净注射液可能通过调节免疫炎症反应发挥抗COVID-19的作用。

Objective:To analyze the mechanism of action of the active ingredients in Xuebijing injection liquid in the treatment of novel coronavirus pneumonia(COVID-19)through immune and anti-inflammatory pathways by using network pharmacological methods to provide theoretical basis for clinical treatment.Methods:The active ingredients in Xuebijing injection were obtained by searching literature,and the active ingredients were screened by TCMSP and DrugBank database and the corresponding targets were predicted.Search for immune and anti-inflammatory targets related to COVID-19 in TTD and DisGeNT databases,map with Xuebijing injection targets to screen out common targets as research targets,and use Cytoscape 3.5.1 software to construct traditional Chinese medicine-components-targets Network diagram;import common targets into the STRING database to construct a protein-protein interaction network diagram.Combine the network diagram to screen the core targets of Biaobijing injection.The GO biological process and KEGG signal pathway enrichment analysis were carried out through the DAVID database.Results:Xuebijing injection has 116 active ingredients,59 key targets,595 interaction relationships,29 of which are key ingredients.There are 541 immune and anti-inflammatory-related targets related to COVID-19.There are 75 common targets in the intersection of Xuebijing and COVID-19,including 55 key protein targets,4 key active ingredients,and 864 interaction relationships.93 GO entries.KEGG pathway analyzes 27 key targets related to inflammation and immunity.The molecular docking results showed that the active ingredients such as purple danshenin C,carnosol,β-sitosterol,danshen quinone D,quercetin,kaempferol,luteolin,baicalein and other active ingredients and SARS-CoV-2 Strong binding ability.Conclusion:Xuebijing injection may exert its anti-COVID-19 effect through multiple components and multiple targets,and its mechanism may be related to the pathways affecting immunity and inflammation.