Abstract
Singapore grouper iridovirus (SGIV) is a highly pathogenic virus that causes substantial economic losses in marine grouper aquaculture, and effective antiviral agents are currently lacking. In this study, the anti‐SGIV activity of epigallocatechin gallate (EGCG), a natural compound from green tea, was evaluated and its underlying mechanisms were investigated. Cytotoxicity assays showed that EGCG at concentrations up to 12.5 μg/mL was safe for grouper spleen (GS) cells. EGCG treatment reduced viral MCP and VP19 mRNA expression in a dose‐dependent manner, indicating its anti‐SGIV activity. Mechanistic studies revealed that EGCG directly impaired SGIV particle infectivity and interfered with viral adsorption, entry, and intracellular replication. Network pharmacology analysis identified overlapping genes between EGCG targets and SGIV‐induced differentially expressed genes, with enrichment pathways related to cell cycle regulation, particularly the G2/M checkpoint. Further studies showed that SGIV infection upregulated the G2/M checkpoint regulators WEE1 and CHEK2, and EGCG treatment reversed these dysregulations, suggesting that EGCG alleviates SGIV‐induced G2/M arrest. In vivo, EGCG treatment significantly reduced viral load in infected groupers and improved survival rate. Collectively, these findings demonstrate that EGCG exerts potent anti‐SGIV activity both in vitro and in vivo by directly targeting multiple steps of the viral life cycle and modulating host cell cycle G2/M checkpoint pathways, highlighting its potential as a natural therapeutic agent against SGIV infection.