Objective:To investigate the potential mechanisms of nonsteroidal anti-inflammatory drugs(NSAIDs)as anti-inflammatory analgesics against respiratory syncytial virus(RSV)through a network pharmacology approach.The most influential NSAIDs against RSV were screened through network pharmacology studies.Methods:NSAIDs(19 active drugs and one prodrug)approved by U.S.Food and Drug Administration(FDA)were used in this study.Targets for NSAIDs were collected through the Swiss Target Prediction and PubChem databases,and RSV targets were searched in the GeneCards database.The intersection of NSAIDs target proteins with RSV target proteins was mapped using Wayne's Web,protein interaction analysis of drug-disease intersection target proteins was performed in the STRING da-tabase,and the network was embellished using Cytoscape 3.9.0.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the intersecting target proteins was performed in the DAVID database.Bubble plotting for KEGG pathway enrichment analysis was made using the Bioinformatics drawing tool.Pathway-target-component net-work analysis was performed by Cytoscape 3.9.0.Finally,the binding affinity of NSAIDs to target proteins is deter-mined by molecular docking(AutoDock Vina).Results:A total of 421 targets of NSAIDs,391 targets associated with RSV,39 overlapping target proteins were collected.37 anti-RSV signaling pathways were revealed busing Genomic en-richment analysis.MAPK1,AKT1 and MAP2K1 were explored as the target proteins with the greatest relevance to the B-cell receptor signaling pathway.Conclusion:Three NSAIDs(sulforaphane,rofecoxib and diclofenac)may block the B-cell receptor signaling pathway by inactivating their related target proteins,thereby potentially alleviating RSV-induced bronchitis and pneumonia.
关键词
非甾体抗炎药(NSAIDs)/呼吸道合胞病毒(RSV)/网络药理学/分子对接/机制研究
Key words
Nonsteroidal anti-inflammatory drugs(NSAIDs)/Respiratory syncytial virus/Network pharmacolo-gy/Molecular docking/Research on mechanisms
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