Synthesis and application of a potential therapeutic coumarin derivative against IHNV in aquaculture

Abstract Infectious haematopoietic necrosis virus (IHNV) is one of the most serious pathogens in aquaculture, causing devastating damage to salmonid. In this study, a novel coumarin derivative (DC) was designed and synthesized to evaluate its anti-IHNV effects in vitro and in vivo. DC at the concentration of up to 10 mg/L significantly inhibited IHNV replication in epithelioma papulosum cyprini (EPC) cells with a maximum inhibitory rate of >95%. Additionally, the results revealed that DC treatment significantly suppressed the IHNV-induced cytopathic effect (CPE) in host cells. Moreover, further data found that DC significantly increased superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) activities, and decreased malondialdehyde (MDA) content in EPC cells and in rainbow trout, suggesting that IHNV-induced antioxidant-oxidant imbalance was inhibited by DC. For in vivo studies, DC exhibited an anti-IHNV effect by substantially enhancing the survival rate of virus-infected fish via intraperitoneal injection. Additionally, DC enhanced the levels of IFN-related genes demonstrated that DC indirectly activated IFNs for the clearance of IHNV in rainbow trout. Importantly, the data showed that horizontal transmission of IHNV was reduced by DC in a static cohabitation challenge model, especially for recipient fish in bath treatment, which suggested that DC might be suitable as a possible therapeutic agent for IHNV in aquaculture.