采用网络药理学和分子对接技术研究血必净注射液抗新冠肺炎的作用机制

目的： 通过网络药理学和分子对接技术，探讨血必净注射液治疗新冠肺炎（COVID-19）的潜在分子机制。方法： 采用中药系统药理学分析平台（TCMSP）数据库收集血必净对应的化合物成分和作用靶点，选用GeneCards数据库获取COVID-19相关靶点；获取血必净注射液与COVID-19的共同作用靶点，采用STRING数据库构建蛋白互作网络图，运用Cytoscape软件对网络图进行可视化分析获取关键靶点；DAVID数据库对共有靶点进行GO （gene ontology）和KEGG （Kyoto encyclopedia of genes and genomes）富集分析，通过Cytoscape软件构建血必净注射液"成分-靶点-疾病"网络图。采用AutoDock Tools对血必净注射液核心成分与SARS-CoV-2 3CL水解酶蛋白和血管紧张素转换酶II （ACE2）进行分子对接，并通过PyMOL软件进行可视化处理。结果： 共筛选出血必净注射液中5种药材对应的270个对应靶点，与COVID-19有52个共表达靶点。GO富集分析得到160个生物过程，KEGG分析得到112条信号通路。分子对接表明，血必净注射液中槲皮素、β-谷甾醇、木犀草素为degree较高的活性成分，与3CL水解酶和ACE2具有较强的结合能力。结论： 血必净注射液可能通过槲皮素、β-谷甾醇、木犀草素等成分调节IL6、CCL2、TNF、PTGS2等核心基因参与COVID-19的治疗，同时也说明血必净注射液可通过"多成分-多靶点-多途径"发挥对COVID-19的治疗作用。

Study on COVID-19 mechanism of Xuebijing injection by network pharmacology and molecular technology

OBJECTIVE To explore the potential molecular mechanism of Xuebijing injection in the treatment of corona virus disease 2019 (COVID-19) through network pharmacology and molecular docking technology.METHODS The TCM System Pharmacology analysis platform (TCMSP) database was used to collect the compound composition and action target of Xuebijing, and the genecards database was used to obtain the COVID-19 related target. The common action target of Xuebijing injection and COVID-19 was obtained, and the protein interaction network diagram was constructed by STRING database. The key targets were obtained by the visualized analysis of the network diagram by the software of Cytoscape. The common targets of Xuebijing injection were enriched by GO (gene ontology) and KEGG (Kyoto encyclopedia of genes and genomes) in DAVID database. The "composition-target-disease" network diagram of Xuebijing injection was constructed by using the software of Cytoscape. Autodock tools was used to dock the core components of Xuebijing injection with SARS-CoV-2 3CL hydrolase protein and ACE2, and PyMOL software was used for visualization.RESULTS A total of 270 corresponding targets corresponding to the five medicinal materials in Xuebijing injection were screened, and 52 co-expressed targets were with COVID-19.GO enrichment analysis resulted in 160 biological processes and KEGG analysis resulted in 112 signaling pathways.Molecular docking showed that quercetin, β-sitosterol and luteolin were the active components with high degree in Xuebijing injection, which had the ability to bind to 3CL hydrolase and ACE2.CONCLUSION Xuebijing injection can regulate IL6, CCL2, TNF, PTGS2 and other core genes through quercetin, β-sitosterol, luteolin and other components to participate in the treatment of COVID-19, which also shows that Xuebijing injection can play the therapeutic role of COVID-19 through "multi-component-multi-target-multi-pathway".