Rhabdoviruses cause devastating diseases in aquaculture, resulting in enormous economic losses. Our previous studies indicated that imidazole arctigenin derivatives possessed antiviral activities against aquatic rhabdoviruses. Based on the data of structure-activity relationship, a new imidazole arctigenin derivative, 4-(8-(2-bromoimidazole)octyloxy)-arctigenin (BOA), was designed and synthesized. And its antiviral activities against aquatic rhabdoviruses (SVCV, IHNV and MSRV) were evaluated in vitro. By comparing inhibitory concentration at half-maximal activity (IC 50), we found that BOA (IC50 = 1.11 μM) possessed a higher anti-IHNV activity than the antiviral imidazole arctigenin derivatives which were found in our previous study. Besides, BOA could cause profound inhibition of SVCV and MSRV replication. By the reduction assays on cytopathic effect, BOA exhibited a protective effect on two host cell lines. As a typical rhabdovirus, SVCV was chosen as a model to illuminate the anti-rhabdovirus mechanism of BOA. BOA was discovered to not impact directly on viral particles or interfere with SVCV adsorption. And it worked within the 2-6 h of the early phase of virus replication. In addition, after repression of cell cycle S phase and recovery of caspase-3/8/9 activities activated by SVCV, BOA inhibited SVCV-induced apoptosis and then reduced the release of viral particles at the late stage of virus replication. Altogether, BOA was expected to be a highly efficient antiviral agent against multiple rhabdoviruses in the field of aquaculture.

中文翻译：

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一种新型牛蒡苷元衍生物对水产养殖中多种弹状病毒的抗病毒活性的评价。

弹状病毒在水产养殖中引起毁灭性的疾病，造成巨大的经济损失。我们之前的研究表明咪唑牛蒡苷衍生物对水生弹状病毒具有抗病毒活性。根据构效关系数据，设计合成了一种新型咪唑牛蒡甙元衍生物4-(8-(2-溴咪唑)辛氧基)-牛蒡甙元(BOA)。并在体外评估了其对水生弹状病毒（SVCV、IHNV 和 MSRV）的抗病毒活性。通过比较半最大活性 (IC 50) 的抑制浓度，我们发现 BOA (IC50 = 1.11 μM) 比我们之前研究中发现的抗病毒咪唑牛蒡苷衍生物具有更高的抗 IHNV 活性。此外，BOA 可能会导致 SVCV 和 MSRV 复制的严重抑制。通过对细胞病变效应的减少测定，BOA 对两种宿主细胞系表现出保护作用。作为典型的弹状病毒，SVCV被选为模型来阐明BOA的抗弹状病毒机制。发现 BOA 不直接影响病毒颗粒或干扰 SVCV 吸附。它在病毒复制早期的 2-6 小时内起作用。此外，在抑制细胞周期 S 期和恢复 SVCV 激活的 caspase-3/8/9 活性后，BOA 抑制 SVCV 诱导的细胞凋亡，然后减少病毒复制后期病毒颗粒的释放。总而言之，BOA有望成为水产养殖领域针对多种弹状病毒的高效抗病毒剂。选择 SVCV 作为模型来阐明 BOA 的抗弹状病毒机制。发现 BOA 不直接影响病毒颗粒或干扰 SVCV 吸附。它在病毒复制早期的 2-6 小时内起作用。此外，在抑制细胞周期 S 期和恢复 SVCV 激活的 caspase-3/8/9 活性后，BOA 抑制 SVCV 诱导的细胞凋亡，然后减少病毒复制后期病毒颗粒的释放。总而言之，BOA有望成为水产养殖领域针对多种弹状病毒的高效抗病毒剂。选择 SVCV 作为模型来阐明 BOA 的抗弹状病毒机制。发现 BOA 不直接影响病毒颗粒或干扰 SVCV 吸附。它在病毒复制早期的 2-6 小时内起作用。此外，在抑制细胞周期 S 期和恢复 SVCV 激活的 caspase-3/8/9 活性后，BOA 抑制 SVCV 诱导的细胞凋亡，然后减少病毒复制后期病毒颗粒的释放。总而言之，BOA有望成为水产养殖领域针对多种弹状病毒的高效抗病毒剂。在抑制细胞周期 S 期和恢复 SVCV 激活的 caspase-3/8/9 活性后，BOA 抑制 SVCV 诱导的细胞凋亡，然后减少病毒复制后期病毒颗粒的释放。总而言之，BOA有望成为水产养殖领域针对多种弹状病毒的高效抗病毒剂。在抑制细胞周期 S 期和恢复 SVCV 激活的 caspase-3/8/9 活性后，BOA 抑制 SVCV 诱导的细胞凋亡，然后减少病毒复制后期病毒颗粒的释放。总而言之，BOA有望成为水产养殖领域针对多种弹状病毒的高效抗病毒剂。