Targeting Peroxiredoxin 6: Tannic Acid Inhibits Singapore Grouper Iridovirus Infection via PRDX6‐Dependent Pathway and Antioxidant Response

ABSTRACT

Singapore grouper iridovirus (SGIV) is a major viral pathogen threatening grouper aquaculture. The lack of specific antiviral drugs underscores the urgent need to develop safe and effective control strategies. This study demonstrates that tannic acid (TA) exhibits significant anti‐SGIV activity in vitro. In grouper spleen (GS) cells, TA inhibited SGIV replication in a concentration‐dependent manner. Time‐of‐addition assays confirmed its antiviral efficacy when applied either before or after SGIV infection. Mechanistically, TA directly interfered with SGIV particle infectivity, viral adsorption, entry and intracellular replication. Network pharmacology analysis suggested TA's targets are associated with host cellular antioxidant pathways, among which Peroxiredoxin 6 (PRDX6) was identified as a potential target of TA. Further experiments confirmed that TA upregulated the Nrf2 antioxidant pathway and suppressed the expression of pro‐inflammatory cytokines (IL‐1β, IL‐8). Notably, TA enhanced the expression of PRDX6, and overexpression of PRDX6 significantly inhibited SGIV replication, indicating that PRDX6 contributes to the antiviral effect of TA. In vivo, TA treatment not only restored PRDX6 expression in infected groupers but also significantly reduced viral load in liver and spleen following SGIV infection. These findings demonstrate that TA inhibits SGIV through direct viral interference and PRDX6‐mediated antioxidant modulation, highlighting its potential as a natural therapeutic agent against SGIV.