4′-(8-imidazole-octyloxy)-arctigenin efficiently inhibits spring viraemia of carp virus infection in vitro and in vivo

Spring viraemia of carp virus (SVCV), an important aquatic rhabdoviruses, causing devastating mortality in various carp species and other cultivated fish. In our previous studies, 4′-(8-Imidazole-octyloxy)-arctigenin (6A) with an eight carbon atoms of linker showed the higher activity against SVCV in EPC cells, based on the structure-activity relationship of 35 arctigenin derivatives. In this study, the antiviral activity and mechanism of 6A was further investigated both in vivo and in vitro. An analysis of survival curve of zebrafish indicated that 6A-treated group increased the survival rate by 23.4% and 20.0% following with 100 and 103 TCID50 doses of SVCV, respectively. Besides, 6A inhibited the gene expression of SVCV nucleoprotein and glycoprotein in brain, spleen, and liver at 4 and 7 d post-infection (dpi) by over 90% and 60%, respectively. Consistent with above results, there were no apparent signs of infection and inflammation in the brain, spleen and liver of the 6A-treated fish. However, we unexpectedly found an inability on 6A-treated zebrafish and EPC cells to mount a strong IFNф1 response to SVCV, which indicated that 6A inhibited SVCV replication not via the activation of IFNф1-related genes. Moreover, pre-treatment, co-treatment, and post-treatment of 6A with SVCV, 6A was observed to possess an intense antiviral response in the early stage of viral infection. Altogether, 6A was expected to be a therapeutic agent for the treatment of SVCV in aquaculture.