An imidazole coumarin derivative enhances the antiviral response to spring viremia of carp virus infection in zebrafish.

As an efficient pathogen resulting in economic impact in aquaculture, spring viremia of carp virus (SVCV) causes devastating disease in cyprinids. Based on the previous study that 7-(6-(2-methyl-imidazole))-coumarin (D5) exhibited anti-SVCV activity in fish cells, we hypothesized that D5 may be useful as a potential therapeutic agent for controlling SVCV infection in vivo. In this study, we verified that D5 inhibited SVCV replication in zebrafish, with reducing 22.5% mortality of SVCV-infected fish. Further data suggested that coumarin D5 was more stable with a prolonged inhibitory half-life in the early stage of virus infection (1-4 days). Consistent with above results, D5 decreased the viral titer in fish body and repressed SVCV glycoprotein gene expression in virus sensitive tissues (kidney and spleen) in the early stage of virus infection. In addition, the results replied that D5 elicited an innate immune response in non-viral infected zebrafish by up-regulating the expression of interferon genes (IFNγ, IFNφ1, IFNφ2 and RIG-1). D5 also enhanced the levels of antioxidant-related gene transcription and enzyme activities in SVCV-infected zebrafish, suggesting that D5 exhibited an antioxidant protection on fish by keeping the balance of redox state. Therefore, D5 is a potential therapeutic agent for the devastating fish rhabdovirus infections.