基于网络药理学和分子对接技术探究金银花入血成分干预新型冠状病毒肺炎的作用机制

Explore mechanism of blood components Lonicerae Japonicae Flos intervening COVID-19 based on network pharmacology and molecular docking technology

目的通过网络药理学和分子对接技术探究金银花入血成分干预新型冠状病毒肺炎(COVID-19)的作用机制。方法通过Swiss Target Prediction和Similarity Ensemble Approach数据库检索金银花中入血成分的作用靶点,利用GeneCards数据库和CTD数据库检索COVID-19靶点基因,利用Cytoscape 3.7.1软件构建金银花入血成分-靶点网络,利用DAVID工具对金银花抗COVID-19靶标基因进行GO生物学过程富集分析,应用KOBAS3.0工具对金银花抗COVID-19靶标基因进行KEGG通路富集分析。结果筛选出金银花10个入血成分金丝桃苷、7-甲氧基香豆素、3-O-阿魏酰奎尼酸、绿原酸、新绿原酸、隐绿原酸、对酞酸二甲酯、癸二酸二丁酯、十六碳烯酸、herboxidiene,可能通过作用于磷酸肌醇3激酶调控亚基1(PIK3R1)、B细胞κ轻肽基因增强子核因子1(NFKB1)、鼠肉瘤病毒癌基因(HRAS)、白细胞介素6(IL6)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)、胱天蛋白酶3(CASP3)、生长因子受体结合蛋白2(GRB2)、糖原合酶激酶3β(GSK3β)、禽肉瘤病毒17的假定转化基因(JUN)、丝裂原活化蛋白激酶10(MAPK10)、丝裂原活化蛋白激酶14(MAPK14)、丝裂原活化蛋白激酶8(MAPK8)等关键靶点干预27条关键信号通路,主要涉及免疫、炎症、病毒、神经系统等相关通路。分子对接结果显示金丝桃苷与新型冠状病毒3CL(SARS-CoV-23CL)水解酶和血管紧张素转化酶2(ACE2)结合最为稳定。结论金银花中入血成分可通过干预与抗炎、抗病毒、免疫、解热、止痛、镇静等相关的蛋白及通路发挥抗COVID-19的作用。

Objective To explore the mechanism of Lonicerae Japonicae Flos(LJF)intervening COVID-19 by network pharmacology and molecular docking.Methods The potential targets of ingredients in serum of LJF were searched by Swiss Target Prediction and Similarity Ensemble Approach platform,and to predict and screen the therapeutic targets of COVID-19 through GeneCards and CTD databases.Ingredients in serum-target pathway network model was established by Cytoscape 3.7.1 software.GO biological process enrichment analysis of anti-COVID-19 target genes in Lonicerae Japonicae Flos was performed by DAVID,and KEGG pathway enrichment analysis of anti-COVID-19 target genes in in serum of Lonicerae Japonicae Flos was performed by KOBAS 3.0.Results Ten ingredients in serum of Lonicerae Japonicae Flos such as hyperoside,7-methoxycoumarin,3-O-feruloylquinic acid,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,dimethyl terephthalate,dibutyl sebacate,hexadecenoic acid,herboxidiene involved in PIK3 R1,NFKB1,HRAS,IL6,TNF,TP53,CASP3,GRB2,GSK3 B,JUN,MAPK10,MAPK14,MAPK8,PRKCA,and affected 27 mainly pathways involved in immune,inflammation,virus,nervous system,and so on.The molecular docking showed that the binding energy of hyperoside with the SARS-CoV-23 CL hydrolase and ACE2 were most stable.Conclusion Ingredients in serum of Lonicerae Japonicae Flos may interfere proteins and pathways related to anti-inflammatory,antiviral immunity,antipyretic,analgesic and sedation to play a role against COVID-19.