In vivo and in vitro antiviral effect and mechanisms of rhein against nervous necrosis virus

Viral nervous necrosis (VNN) caused by nervous necrosis virus (NNV) is a major threat to the global aquaculture industry, resulting in huge economic losses. In this study, we evaluated a naturally anthraquinone, rhein, as a potential therapeutic agent against NNV. Rhein effectively inhibited NNV-induced cytopathic effects (CPE) at a concentration of 18.84 μM, with an inhibitory concentration (IC 50 ) against NNV replication of 8.77 μM. Moreover, the study revealed a possible anti-NNV mechanism. Rhein could disrupt NNV-induced S-phase cell cycle arrest by inhibiting ATP synthesis, and cell cycle arrested in S phase is favorable for NNV replication, which in turn inhibits NNV replication. The therapeutic effect of rhein was also evaluated in vivo , where the survival rate of NNV infected grouper was increased by 26.7% with the treatment of 10 mg/kg rhein. Our findings demonstrated the potential of rhein as a pharmacological compound that exerts significant antiviral activity against NNV by modulating the cell cycle and ATP synthesis. Consequently, rhein has shown significant promise as a medication for the prevention and treatment of viral infections in aquaculture.