Antiviral activity of curcumin against Israeli acute paralysis virus in Apis mellifera: Screening and mechanistic study.

The Israeli acute paralysis virus (IAPV), widespread in honeybee (Apis mellifera) colonies, causes paralysis, tremors, and eventual mortality, while strongly associated with colony collapse disorder (CCD). Currently, there are no widely approved antiviral therapies for IAPV infection; however, several natural compounds have shown promising antiviral efficacy. In this study, we evaluated the effects of eight natural compounds (myrcene, citral, menthol, chlorogenic acid, resveratrol, curcumin, quercetin, and tea polyphenols) on IAPV-infected honeybees. Bees were artificially or naturally infected with IAPV and subsequently fed sucrose solution supplemented with these compounds. Quantitative RT-PCR analysis revealed that curcumin was the most effective compound in reducing viral load. After seven days of treatment with 10 µM curcumin, IAPV levels decreased by 46.2 % in artificially infected bees and 84.0 % in naturally infected bees. Transcriptomic analysis showed that curcumin upregulated genes involved in nutritional metabolism (e.g., Vg) and the RNA interference (RNAi) pathways (e.g., dicer, hsp90), which play a critical role in antiviral defense. Interestingly, it downregulated antimicrobial peptide genes (hymenoptaecin, abaecin, defensin 1). These findings demonstrated that curcumin mediated a strategic immune reconfiguration in honeybees, concentrating more resources on the RNAi pathway, while reducing energetically costly antimicrobial peptide synthesis. This optimized antiviral defense, combined with improved vitellogenin expression, suggests a metabolic efficiency adaptation that preferentially directs resources toward more effective IAPV countermeasures. Our results suggest that curcumin is a dual-action therapeutic candidate that simultaneously strengthens crucial antiviral defenses and maintains host vitality, offering significant promise for sustainable honeybee health management.