Anti-COVID-19 active ingredients and mechanism of Lonicerae Japonicae Flos based on network pharmacology and molecular docking
Objective To explore the potential mechanism of Lonicerae Japonicae Flos against COVID-19 by combining the chemical composition of Lonicerae Japonicae Flos with network pharmacology study.Methods The chemical constituents of Lonicerae Japonicae Flos were qualitatively analyzed by UPLC-Q-Exactive/MS.The chemical constituents of Lonicerae Japonicae Flos were identified according to the peak retention time,exact molecular mass,characteristic fragment ions,and related literature data.The targets of constituents were obtained by SWISS Target Prediction database,the disease targets of COVID-19 were obtained by GeneCard and OMIM database,the common pharmacodynamic targets of Lonicerae Japonicae Flos and COVID-19 were obtained by Venny 2.1.0,and the"constituent-target"network was constructed by Cytoscape 3.7.2 software.The protein-protein interaction(PPI)network was constructed by STRING database,and the GO analysis and KEGG analysis were performed on the targets.The molecular docking technology was used to verify the binding ability of core targets and corresponding constituents.The potential mechanism of chlorogenic acid in Lonicerae Japonicae Flos against COVID-19 was verified by in vitro antiviral test.Results A total of 77 chemical constituents were identified from Lonicerae Japonicae Flos in vitro.Caffeic acid,adenosine,chrysoeriol 5-methyl ether,apigenin and ferulic acid,may be the active components of Lonicerae Japonicae Flos against COVID-19.Epidermal growth factor receptor(EGFR)and interleukin-2(IL2)were the key targets,involving hypoxia inducible factor-1(HIF-1)signaling pathway,phosphatidylinositol 3-kinase-protein kinase B(PI3K-AKT)signaling pathway.Further molecular docking results showed that the five key active components of Lonicerae Japonicae Flos and the two core targets of the disease had good binding activity,and the binding energy values were less than-20.9 kJ·mol-1.At the same time,chlorogenic acid,the main effective component of Lonicerae Japonicae Flos,had good in vitro inhibitory activity against 3CLpro[IC50 was(106.40±0.71)μmol·L-1].Conclusions Lonicerae Japonicae Flos may inhibit COVID-19 through multiple targets such as EGFR,IL2 and 3CLpro,which can provide a valuable basis for further research on the mechanism of Lonicerae Japonicae Flos against COVID-19.
万方数据
