Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Respiratory syncytial virus (RSV), a single-stranded negative-sense RNA virus, is a major pathogen of acute respiratory tract infections, posing severe threats to the health of infants, the elderly and immunocompromised individuals. While approved vaccines for older adults and monoclonal antibody prophylaxis for infants are available, effective therapeutic drugs remain scarce. Resveratrol, a phenolic compound naturally present in grapes, berries and other foods, has been confirmed to exhibit anti-RSV activity, but its molecular mechanism of action remains unclear. Objectives: This study aimed to screen the core targets and key signaling pathways of resveratrol against RSV using computational biology approaches, propose testable research hypotheses and provide a theoretical basis for subsequent experimental validation. Methods: A total of 261 resveratrol-related targets and 1196 RSV-related targets were retrieved from databases. Venny 2.1.0 was used to identify 67 overlapping targets, which were then subjected to protein-protein interaction (PPI) network construction via STRING/Cytoscape and topological analysis for core target screening. GO/KEGG enrichment analyses were performed using the DAVID database and molecular docking validation was conducted with PyMOL/AutoDock. Results: Ten core targets including EGFR, SRC, HSP90AA1 and ALB were identified. GO enrichment focused on biological processes such as PI3K-Akt signal transduction and MAPK cascade regulation, while KEGG pathways were enriched in the Ras signaling pathway and others. Molecular docking showed stable binding of resveratrol to core targets, with all binding energies <-5 kcal/mol. Conclusion: This in-silico study predicts that resveratrol may exert anti-RSV effects by targeting host proteins such as EGFR and SRC and regulating key pathways including PI3K-Akt and Ras, complementing existing evidence of its direct interaction with viral proteins. The study provides novel insights for anti-RSV drug development and a theoretical foundation for subsequent experimental validation.