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新型牛蒡子苷元衍生物对水产呼肠孤病毒的体外和体内抑制作用。

In vitro and in vivo inhibition of a novel arctigenin derivative on aquatic rhabdovirus.

机构信息

College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi 712100, China.

Changzhou Agricultural Comprehensive Technology Extension Center, Middle Changjiang Road 289-1nd, Changzhou, Jiangsu 213002, China.

出版信息

Virus Res. 2022 Jul 15;316:198798. doi: 10.1016/j.virusres.2022.198798. Epub 2022 May 11.

DOI:10.1016/j.virusres.2022.198798
PMID:35562080
Abstract

Spring viraemia of carp virus (SVCV) poses a serious threat to aquaculture industry due to the lack of approved antiviral treatments. Therefore, a novel arctigenin derivative, 4-(2-methylimidazole) octanoxy-arctigenin (MON), was synthesized to assess the antiviral activity against SVCV in vitro and in vivo. The results indicated MON decreased the SVCV glycoprotein (G) gene expression in vitro by a maximum inhibitory rate of > 99% at 3.5 μM. Furthermore, MON showed the protective effect on epithelioma papulosum cyprinid (EPC) cells and considerably decreased the cytopathic effect (CPE). More importantly, MON inhibited SVCV G gene expression levels in vitro at the half-maximal activity (IC) of 0.18 μM at 48 h. For in vivo studies, MON demonstrated anti-SVCV activity by enhancing the survival rate of zebrafish (Danio rerio) after infection via pelvic fin base injection. These results tended to be consistent with MON decreasing the SVCV titer of infected zebrafish. During this time, viral loads of the spleen and kidney have declined in SVSV-infected zebrafish. Based on the histopathological assay, MON exhibited the high protective effect in the spleen and kidney of SVCV-infected fish. Combined, MON is on track to become a novel agent to address SVCV infection in aquaculture.

摘要

锦鲤疱疹病毒(SVCV)由于缺乏批准的抗病毒治疗方法,对水产养殖业构成严重威胁。因此,合成了一种新型的牛蒡子苷元衍生物 4-(2-甲基咪唑基)辛氧基牛蒡子苷元(MON),以评估其在体外和体内抗 SVCV 的活性。结果表明,MON 在 3.5 μM 时最大抑制率>99%,可降低 SVCV 糖蛋白(G)基因的体外表达。此外,MON 对鲤鱼上皮瘤细胞(EPC)具有保护作用,并显著降低细胞病变效应(CPE)。更重要的是,MON 在 48 小时时以半最大活性(IC)0.18 μM 抑制 SVCV G 基因的表达。在体内研究中,通过经腹鳍基部注射感染,MON 提高了斑马鱼(Danio rerio)的存活率,从而显示出抗 SVCV 活性。这些结果与 MON 降低感染斑马鱼中 SVCV 滴度的趋势一致。在此期间,感染 SVSV 的斑马鱼的脾脏和肾脏中的病毒载量下降。基于组织病理学检测,MON 对 SVCV 感染鱼的脾脏和肾脏具有很高的保护作用。综合来看,MON 有望成为解决水产养殖中 SVCV 感染的新型药物。

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