Anti-respiratory syncytial virus effect of Gardeniae Fructus and investigation of mechanism based on network pharmacology and molecular docking
Objective To study the anti-respiratory syncytial virus(RSV)effect of Gardeniae Fructus and predict its mechanism.Methods To explore the inhibitory effect of Gardeniae Fructus on respiratory syncytial virus(RSV)through drug cytotoxicity assay,cytopathic effect(CPE)and real-time fluorescence quantitative PCR(qRT-PCR)assay;to search for the active ingredients of Gardeniae Fructus and predict its targets in TCMSP,and to obtain the relevant targets of RSV from GeneCards,OMIM and Disgen databases;to construct key protein-protein interactions after obtaining drug-virus intersection genes.RSV related targets were obtained from GeneCards,OMIM,and Disgen databases,and the drug-virus intersection genes were obtained to construct a key protein-protein interaction(PPI)network and validated by molecular docking;the intersection genes were analyzed by Gene Ontology Functional Enrichment(GO)analysis via the DAVID database,and the mechanism of action was predicted by the Kyoto Encyclopedia of Genes and Genomes(KEGG)-based pathway enrichment analysis.Results The half cytotoxicity concentration(TC50)of Gardeniae Fructus extract was 4.621 mg·mL-1,and significant anti-RSV effects were observed at mass concentrations of 3.543 8,1.771 9,and 0.886 0 mg·mL-1,and with the increase of the mass concentration,the anti-RSV effects were stronger.A total of 10 effective compounds of Gardeniae Fructus were screened by network pharmacology(OB ≥ 30％,DL＞0.18),and the visualization results showed that there were 118 nodes,and the main targets were AKT1,SRC,and EGFR,etc.;GO results showed that they were mainly related to the processes of positive regulation of protein kinase B signaling,and protein phosphorylation;the plasma membrane,and the macromolecule complex;and the processes of ATP-binding,enzyme-binding,and protein kinase activity.processes.KEGG pathway was enriched to 117 signaling pathways(FDR＜0.01),which were mainly related to PD-L1 expression and PD-1 checkpoint pathway,phosphatidylinositol 3-kinase/protein kinase B(P13K-Akt),and C-type lectin receptors(CLRs)signaling pathways in tumors.Conclusion Gardeniae Fructus extract has significant anti-RSV effects,which may be mainly based on the combination of components such as soy sterol,β-glutamate,and saffronic acid with targets such as EGFR,SRC,and MAPK3,and exerts its anti-respiratory syncytial virus effects through the signaling pathways such as PD-L1 expression and the PD-1,PI3K-Akt,and CLRs pathways.
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