Gallic acid and luteolin-based self-assembled nanoparticles alleviate white spot syndrome virus infection in Procambarus clarkii

White Spot Syndrome Virus (WSSV) is a major viral pathogen severely threatening crustacean aquaculture. Although natural products possess antiviral potential, their application remains limited due to stability and utilization constraints. This study employed a self-assembly strategy to construct a natural product-based metal-organic nanostructure of luteolin-loaded magnesium-gallic acid (Mg-GA) metal-organic framework (LM), to enhance the anti-WSSV efficacy of luteolin. Results indicate that the prepared LM exhibits a regular prismatic nanostructure with uniform particle size distribution, stable coordination structure, and good biocompatibility. In vivo experiments demonstrated that compared to single luteolin or Mg-GA treatment groups, LM significantly reduced WSSV viral copy numbers in infected crayfish Procambarus clarkii and markedly improved host survival rates. Gene expression analysis revealed that this self-assembled nanomaterial significantly downregulated expression of key viral genes IE1 , DNApol , and VP28 , while upregulating host antioxidant-related genes CAT and SOD , apoptosis-regulating genes BI-1 , and downregulating apoptosis-regulating genes BAX , inflammation-related genes COX1 and COX2 . This indicates its ability to synergistically inhibit viral replication and enhance host defense capabilities. Histopathological results further confirmed that LM effectively alleviated pathological damage caused by WSSV to gill and intestinal tissues, with no apparent toxicity observed in healthy individuals. In summary, the self-assembled natural product metal-organic nanostructure significantly enhances the anti-WSSV efficacy of single compounds, offering a novel nanostrategy for controlling viral diseases in aquaculture.