Highly efficient inhibition of infectious hematopoietic necrosis virus replication mediated by a novel synthesized coumarin derivative in vitro and in vivo

Abstract

As an efficient pathogen resulting in economic impact in aquaculture, infectious hematopoietic necrosis virus (IHNV) causes devastating disease in salmons. In this study, we designed and synthesized a novel coumarin derivative, 7-((4-aminophenyl)diazenyl)-4-methyl-coumarin (AMC), to evaluate its in vitro and in vivo anti-IHNV effects. The results showed that up to 25 mg/L AMC inhibited the expression of six IHNV protein genes in epithelioma papulosum cyprini (EPC) cells, with a maximum inhibitory rate of >90%. Furthermore, AMC inhibited EPC cell apoptosis induced by IHNV and kept the normal cellular morphological structure, reflecting in the protection of EPC cells from cell swelling, the formation of apoptotic bodies, the disappearance of cellular morphology and nuclear fragmentation. For in vivo study, AMC exhibited an anti-IHNV effect in the virus-infected fish by substantially enhancing the survival rate. Consistent with above results, AMC repressed IHNV gene expression in virus sensitive tissues (brain, kidney and spleen) in the early stage of virus infection. Meanwhile, up-regulation of four interferon (IFN) related gene expressions demonstrated that AMC may activate IFN-related expressions for inhibiting IHNV replication during the early stage of viral infection, which is beneficial for the continuous antiviral action on controlling low viral loads in rainbow trout juvenile. Thus, AMC effectively regulated IHNV-induced undesirable conditions to be an excellent potential therapeutic agent against IHNV infection.