Self-Assembled Curcumin–Epigallocatechin Gallate Nanoparticles Enhance Antiviral Activity Against White Spot Syndrome Virus Through Immunomodulation, Antioxidant Effects, and Metabolic Regulation

White Spot Syndrome Virus (WSSV) remains a major factor limiting the sustainable development of crustacean aquaculture, creating an urgent need to develop comprehensive antiviral strategies with multiple protective functions. Natural bioactive compounds with antiviral, immunomodulatory, and antioxidant activities hold great potential for application; however, their poor stability and low bioavailability limit their practical use. In this study, self-assembled nanosystem (CE SA) composed of epigallocatechin gallate (EGCG) and curcumin (Cur) was constructed based on noncovalent interactions, and its protective effects against WSSV-infected Procambarus clarkii were systematically evaluated. The results indicate that CE SA exhibits good stability, sustained-release properties, and biosafety. Compared with Cur, EGCG, and their physical mixture (CE), CE SA significantly improved the survival rate of infected shrimp and reduced viral copy numbers as well as the expression levels of key viral genes such as IE1, DNApol, and VP28. At the same time, CE SA significantly promoted the expression of relevant genes such as Dorsal, Relish, SOD, and CAT, increased SOD and CAT enzyme activities and hematopoietic cell viability, and effectively alleviated damage to the hepatopancreas and intestinal tissues. Furthermore, metabolomic analysis indicated that CE SA regulates key metabolic processes such as amino acid metabolism, inflammation-related metabolism, nucleotide metabolism, and redox homeostasis, further elucidating its potential mechanism for enhancing the host’s antiviral capacity. In summary, by enhancing the stability and utilization efficiency of natural bioactive components, CE SA achieves superior anti-WSSV efficacy compared to individual components. Its protective effects are closely related to the inhibition of viral replication, enhancement of the immune response, improvement of antioxidant defenses, and regulation of host metabolic homeostasis. This study provides a promising, self-assembling nanostructure strategy for the green prevention and control of viral diseases in aquatic animals.