Fraxetin as a promising natural agent for controlling white spot syndrome virus: Mechanistic insights and application potential

Against the backdrop of the rapid growth of the global crustacean aquaculture industry and the increasingly complex and variable farming environments, White Spot Syndrome Virus (WSSV) has emerged as a major bottleneck in the industry, causing White Spot Disease (WSD) and resulting in significant economic losses annually. However, effective control strategies for this highly contagious viral disease are currently lacking. This study focuses on exploring natural medicinal resources and identifies Fraxinus chinensis Roxb. from 20 medicinal herbs as an effective inhibitor of WSSV proliferation. Its active compound, fraxetin, demonstrated excellent inhibitory effects (97.29 %, 75 mg/kg). Further studies have shown that fraxetin can effectively reduce viral replication in a concentration-dependent manner, downregulate viral gene transcription levels, and significantly increase the survival rate of crayfish infected with WSSV. Additionally, in both preventive/therapeutic administration and static cohabitation models, fraxetin effectively suppresses viral load and blocks horizontal transmission of WSSV, demonstrating its potential as a broad-spectrum control strategy. Mechanistically, fraxetin initially interferes with the expression of viral genes that play a crucial role in initiating WSSV transcription. It also weakens the viral genes' ability to hijack innate immune signaling pathways, thereby disrupting the viral replication cycle. Furthermore, fraxetin modulates various enzyme activities, effectively balancing oxidative stress and inflammatory damage triggered by WSSV infection, promoting the restoration of protein homeostasis, and enhancing its antiviral efficacy within crayfish. Given the established biosynthetic basis for fraxetin, this study provides a solid theoretical foundation for its use as an effective candidate to control WSSV outbreaks, promising significant contributions to the sustainable development of the aquaculture industry.