基于网络药理学及分子对接技术探讨血必净注射液治疗新型冠状病毒肺炎的潜在靶标及机制

Exploring the potential targets and mechanisms of Xuebijing Injection for COVID-19 based on network pharmacology and molecular docking technology

目的采用网络药理学和分子对接的方法探讨血必净注射液治疗新型冠状病毒肺炎(COVID-19)的潜在调控机制。方法借助中药系统药理学数据库与分析平台(TCMSP)获得血必净注射液所有有效活性成分的干预靶点,并与GeneCards数据库、OMIM数据库、PharmGkb数据库、TTD数据库和DrugBank数据库中COVID-19基因相关靶标使用R编程语言取交集,从而获得血必净注射液治疗COVID-19的核心靶标;利用Cytoscape 3.7.2软件构建中药-化合物-靶标网络;通过STRING得到交集靶标的PPI网络;运用数据包进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,预测重叠靶点的作用机制。最后,应用分子对接技术,将关键有效活性成分和PPI中核心蛋白进行分子对接。结果GO功能富集分析包括1818个生物过程(biological process,BP),20种细胞组分(cel‐lular component,CC)以及89种分子功能(molecular function,MF)。前30条KEGG相关通路涉及炎症和免疫反应等,如类风湿性关节炎信号通路、IL-17信号通路、Th17细胞分化通路、缺氧诱导因子(HIF)-1信号通路、JAK-STAT信号通路、炎症性肠病信号通路、NF-κB信号通路等。槲皮素、隐丹参酮、木犀草素、β胡萝卜素可影响IL1B、STAT3、AKT1、VEGFA等重叠靶点,同时,槲皮素可能通过IL1B结合,发挥抗炎、抗病毒和免疫应答作用,治疗COVID-19。结论本研究揭示了血必净注射液中的化学成分通过与关键靶蛋白结合涉及多种生物学过程及通路治疗COVID-19。

Objective To explore the potential regulatory mechanism of Xuebijing injection in the treatment of COVID-19 by using network pharmacology and molecular docking methods.Methods ingredients of Xuebijing injection were obtained by using the pharmacological database and analysis platform of TCM System(TCMSP). And intersections with the COVID-19 gene-related targets in GeneCards database, OMIM database, PharmGkb database, TTD database and DrugBank database using the R programming language. Thus, the core target of Xubijing injection in COVID-19 treatment was obtained;Cytoscape 3.7.2 software was used to construct TCM-compound-target network;PPI network of intersection target was obtained by STRING;Utilized data packets to perform gene ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis to predict the mechanism of overlapping targets. Finally, molecular docking technology was implemented to dock key active ingredients with PPI core protein.Results components(CC) and 89 molecular functions(MF). The first 30 KEGG related pathways involved inflammation and immune response, such as rheumatoid arthritis signaling pathway, IL-17 signaling pathway, Th17 cell differentiation pathway, hypoxiainducible factor(HIF-1) signaling pathway, JAK-Stat signaling pathway, inflammatory bowel disease signaling pathway, NF-κB signaling pathway, etc. Quercetin, cryptotanshinone, luteolin, β-carotene can affect IL1B, STAT3, AKT1, VEGFA and other overlapping targets. Meanwhile, quercetin may exert anti-inflammatory, antiviral and immune responses through IL1B binding to treat COVID-19.Conclusion This study reveals that chemical components in Xuebijing injection are involved in multiple biological processes and pathways in COVID-19 treatment through binding to key target proteins.