Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, 315211, China; Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, 315211, China.
College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi, 712100, China.
Fish Shellfish Immunol. 2018 Dec;83:386-396. doi: 10.1016/j.fsi.2018.09.054. Epub 2018 Sep 21.
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.
香豆素形成了一类具有潜在抗病毒治疗前景的天然存在的化合物精英群体。在之前的研究中，我们设计并合成了香豆素衍生物 7-(4-苯并咪唑-丁氧基)-香豆素（BBC），以评估其对鲤鱼春血病病毒（SVCV）的抗病毒活性。在本研究中，我们的结果表明 BBC 不影响病毒从内体到细胞质的粘附和传递，这表明 BBC 在病毒感染的早期阶段没有抑制活性。进一步的数据确定 BBC 显著降低 SVCV 感染的细胞凋亡并恢复半胱天冬酶-3/8/9 活性。为了揭示 BBC 影响 Nrf2 易位的途径，我们检查了 BBC 处理的 EPC 细胞中蛋白激酶 C（PKC）的变化。我们观察到 BBC 导致 PKCα/β的磷酸化增加，这涉及到红细胞 2 相关因子 2（Nrf2）磷酸化的激活，有利于 Nrf2 在 24 和 48 小时转移到核内。此外，结果表明 BBC 还上调了抗病毒反应、血红素加氧酶-1（HO-1）表达和细胞 IFN 反应。总的来说，这种作用机制为治疗 SVCV 感染提供了一个新的治疗靶点，这些结果表明 BBC 的治疗可有效降低 SVCV 感染，并对 SVCV 诱导的不良情况进行不同的调节。
