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体内试验中香豆素衍生物对鲤春病毒血症病毒的抗病毒效率。

Antiviral efficiency of a coumarin derivative on spring viremia of carp virus in vivo.

机构信息

School of Chemistry & Chemical Engineering, Zhoukou Normal University, Zhoukou, 466001, Henan, China.

School of Chemistry & Chemical Engineering, Zhoukou Normal University, Zhoukou, 466001, Henan, China.

出版信息

Virus Res. 2019 Jul 15;268:11-17. doi: 10.1016/j.virusres.2019.05.007. Epub 2019 May 13.

DOI:10.1016/j.virusres.2019.05.007
PMID:31095989
Abstract

Spring viraemia of carp (SVC) in aquaculture is challenging because there are few preventative measures and/or treatments. The previous study demonstrated that an antiviral coumarin derivative, 7-(4-(4-methyl-imidazole))-coumarin (C2), inhibits spring viremia of carp virus (SVCV) infection by targeting Nrf2-ARE signaling pathway in fish cells. Thus, we hypothesized whether C2 may be used as a potential therapeutic agent for controlling SVCV infection in aquaculture. In this study, SVCV infectivity was significantly inhibited in vitro in a dose-dependent manner by preincubation with C2. C2 was verified against SVCV in zebrafish, in which the mortality and viral titer in fish body were decreased. Like other coumarins, C2 was stable with a prolonged inhibitory half-life (3.5 days) at 15 °C in the early stage of SVCV infection. The results show that horizontal transmission of SVCV was reduced by C2 in a static cohabitation challenge model, especially for recipient fish in injection treatment, which suggested that C2 may be suitable as a possible therapeutic agent for SVCV in aquaculture. Overall, this study provides the new insight that a small molecule antiviral drug can be used to control rhabdovirus infection in fish aquacultures.

摘要

水产养殖中的鲤鱼春病毒血症(SVC)是一个具有挑战性的问题,因为目前几乎没有预防措施和/或治疗方法。先前的研究表明,一种抗病毒香豆素衍生物,7-(4-(4-甲基-咪唑))-香豆素(C2),通过靶向鱼类细胞中的 Nrf2-ARE 信号通路来抑制鲤鱼春病毒血症病毒(SVCV)感染。因此,我们假设 C2 是否可以用作控制水产养殖中 SVCV 感染的潜在治疗剂。在这项研究中,C2 通过与 SVCV 预先孵育,以剂量依赖的方式在体外显著抑制 SVCV 的感染力。C2 在斑马鱼中针对 SVCV 进行了验证,在该实验中,鱼体中的死亡率和病毒滴度降低。与其他香豆素一样,C2 在 SVCV 感染早期在 15°C 下具有延长的抑制半衰期(3.5 天),因此非常稳定。结果表明,C2 在静态共栖挑战模型中减少了 SVCV 的水平传播,尤其是在注射治疗的接受鱼中,这表明 C2 可能适合作为水产养殖中 SVCV 的一种潜在治疗剂。总的来说,这项研究提供了新的见解,即小分子抗病毒药物可用于控制鱼类水产养殖中的弹状病毒感染。

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