Quinoline, with the active site of 8-hydroxyl, efficiently inhibits Micropterus salmoides rhabdovirus (MSRV) infection in vitro and in vivo

Quinoline, with the active site of 8-hydroxyl, efficiently inhibits Micropterus salmoides rhabdovirus (MSRV) infection in vitro and in vivo
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DOI:
10.1111/jfd.13615
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发表时间:
2022-04-21
影响因子:
2.5
通讯作者:
Wang, Gao-Xue
Wang, Gao-Xue
中科院分区:
农林科学3区
文献类型:
--
作者:
Li, Bo-Yang;Yang, Fei;Wang, Gao-Xue

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鲑鱼弹状病毒(MSRV)是一种重要的病原体,会导致鲈鱼养殖业的高死亡率和相关经济损失。迄今为止,尚无有效或经批准的治疗方法。在本研究中,我们评估了 22 种喹啉衍生物在草鱼卵巢 (GCO) 细胞中的抗 MSRV 作用。在这些化合物中,8-羟基喹啉对降低MSRV核蛋白基因表达水平表现出99.3%的有效抑制作用,48小时时的半最大抑制浓度(IC50)值为4.66 μM。此外,8-羟基喹啉通过减少细胞病变效应(CPE)显着增强对 GCO 细胞的保护作用。通过比较22种喹啉衍生物的抗MSRV活性,我们发现8-羟基喹啉具有8-羟基的有效活性位点,可以在体外抑制MSRV感染。对于体内研究,腹腔注射 8-羟基喹啉对感染 MSRV 的大口黑鲈表现出抗病毒作用,使存活率大幅提高 15.0%。重要的是,感染后第三天,受感染的大口黑鲈脾脏中的病毒载量显着减少。总体而言,8-羟基喹啉被认为是水产养殖中对抗 MSRV 的有效药剂。
Micropterus salmoides rhabdovirus (MSRV) is an significant pathogen that causes high mortality and related economic losses in bass aquaculture. There is no effective or approved therapy to date. In this study, we evaluated the anti-MSRV effects of 22 quinoline derivatives in grass carp ovary (GCO) cells. Among these compounds, 8-hydroxyquinoline exhibited valid inhibition in decreasing MSRV nucleoprotein gene expression levels of 99.3% with a half-maximal inhibitory concentrations (IC50) value of 4.66 mu M at 48 h. Moreover, 8-hydroxyquinoline significantly enhanced a protective effect in GCO cells by reducing the cytopathic effect (CPE). By comparing the anti-MSRV activity of 22 quinoline derivatives, we found that 8-hydroxyquinoline possessed the efficient active site of 8-hydroxyl and inhibited MSRV infection in vitro. For in vivo studies, 8-hydroxyquinoline via intraperitoneal injection exhibited an antiviral effect in MSRV-infected largemouth bass by substantially enhancing the survival rate by 15.0%. Importantly, the viral loads in the infected largemouth bass notably reduced in the spleen on the third days post-infection. Overall, 8-hydroxyquinoline was considered to be an efficient agent against MSRV in aquaculture.