Therapeutic potential of phenylpropanoid-based small molecules as anti-SVCV agents in aquaculture

Spring viremia of carp (SVC) is caused by spring viremia of carp virus (SVCV) and contributes to mass cyprinid mortality and enormous economic losses. Until now, there is no licensed therapeutic agents available for controlling SVCV infection, and all aquatic organisms are destroyed to eradicate the virus in affected ponds. In this study, a total of 15 phenylpropanoid derivatives were designed and synthesized for evaluating the anti-SVCV activity. In comparison, 4-phenyl-2-thioxo-1,2,3,4-tetrahydro-5H- chromeno[4,3-d]pyrimidin-5-one (S5) were the highest inhibition of SVCV replication up to 97% in epithelioma papulosum cyprini (EPC) cells. We revealed that S5 treatment significantly suppressed the SVCV-induced cytopathic effect (CPE) and mitochondria injury in EPC cells via protecting mitochondrial functions that maintaining the level of mitochondrial membrane potential (Delta Psi m). Further data showed that S5 significantly increased superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) activities, and decreased malondialdehyde (MDA) content in vitro and in vivo, suggesting that SVCV-induced antioxidant-oxidant imbalance was inhibited by S5. Meanwhile, the data of in vivo study indicated that S5 induced up-regulation of interferon-related gene expression by increasing innate immune responses of zebrafish. As the consequence, intraperitoneal injection of S5 enhanced the survival rate of virus-infected fish. Overall, S5 is expected to be a potential therapeutic agent against SVCV infection in aquaculture.