Antiviral effect of 7-(4-benzimidazole-butoxy)-coumarin on rhabdoviral clearance via Nrf2 activation regulated by PKCα/β phosphorylation.

Coumarin forms an elite class of naturally occurring compounds that possess promising antiviral therapeutic perspectives. In the previous study, we designed and synthesized a coumarin derivative, 7-(4-benzimidazole-butoxy)-coumarin (BBC), to evaluate its antiviral activity on spring viraemia of carp virus (SVCV). In this study, our results show that BBC does not affect viral adhesion and delivery from endosomes to the cytosol, indicating BBC has no inhibitory activity in the early stage of viral infection. Further data are determined that BBC significantly declines SVCV-infected apoptosis and recovers caspase-3/8/9 activity. To reveal the pathway that affects Nrf2 translocation by BBC, we examine changes in protein kinase C (PKC) in EPC cells treated with BBC. We observe that BBC results in a higher phosphorylation of PKCα/β that is involved in the activation of erythroid 2-related factor 2 (Nrf2) phosphorylation to favor Nrf2 translocation to nucleus at 24 and 48 h. In addition, the results show that BBC also up-regulates both antiviral responses, heme oxygenase-1 (HO-1) expression and cellular IFN response. Overall, this mechanism of action provides a new therapeutic target for the treatment of SVCV infection, and these results suggest that treatment with BBC is effective in reducing SVCV infection and differently regulates SVCV-induced undesirable conditions.