Evaluation of Antiviral and Immunomodulatory Effects of Resveratrol in Porcine Reproductive and Respiratory Syndrome by Network Pharmacology and Molecular Docking

Abstract

Aims: To elucidate the therapeutic mechanisms of resveratrol against Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) through an integrated network pharmacology and molecular docking approach, focusing on its potential immunomodulatory and antiviral targets in host cells. Study Design: Computational systems pharmacology study integrating network pharmacology, protein–protein interaction analysis, pathway enrichment, and molecular docking. Methodology: Resveratrol-associated targets were retrieved from SwissTargetPrediction, BindingDB, ChEMBL, TCMSP, and STITCH databases, while PRRS-associated host targets were obtained from the Host–Pathogen Interaction Database (HPIDB). Intersecting targets were used to construct a protein–protein interaction (PPI) network using STRING and visualized in Cytoscape to identify hub genes. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using ShinyGO to determine biological processes and signaling pathways. Five key hub genes that are ISG15, STAT1, TLR3, IL6, and DDX58 were selected for molecular docking using AutoDock to evaluate resveratrol’s binding affinity with these targets. Results: The integrated analysis identified five major hub genes associated with resveratrol’s potential antiviral effects. Docking results showed favorable binding affinities with the following energies: ISG15: −7.53 kcal/mol, DDX58: −7.31 kcal/mol, TLR3: −6.63 kcal/mol, STAT1: −5.45 kcal/mol, IL6: −5.10 kcal/mol, and pathway enrichment revealed significant associations with Toll-like receptor signaling, C-type lectin receptor signaling, and viral infection–related pathways, suggesting resveratrol’s ability to modulate innate immune responses and antiviral signaling cascades. Conclusion: This study demonstrates that resveratrol may exert antiviral and immunomodulatory effects against PRRSV by targeting key immune genes and regulating innate antiviral pathways. These findings provide mechanistic insights into resveratrol’s therapeutic potential as a host-directed antiviral agent for controlling PRRS in swine.