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Tetrandrine inhibits IHNV replication and improves rainbow trout survival likely by targeting Asp-81 on viral phosphoprotein

文献类型： 外文期刊

作者： Wu, Min 1 ; Shao, Yi-zhi 1 ; Lu, Tong-yan 1 ; Lv, Ai-jun 3 ; Xu, Li-ming 1 ; Zhao, Jing-zhuang 1 ;

作者机构： 1.Chinese Acad Fishery Sci, Heilongjiang River Fisheries Res Inst, Harbin 150070, Peoples R China

2.Key Lab Aquat Anim Dis & Immune Technol Heilongjia, Harbin 150070, Peoples R China

3.Tianjin Agr Univ, Coll Fisheries, Tianjin 300384, Peoples R China

关键词： Infectious hematopoietic necrosis virus; Tetrandrine; Anti-viral effect; Viral replication; Phosphoprotein

期刊名称：AQUACULTURE （ 影响因子：3.9； 五年影响因子：4.4 ）

ISSN： 0044-8486

年卷期： 2026 年 611 卷

页码：

收录情况： SCI

摘要： Infectious hematopoietic necrosis (IHN) caused by infectious hematopoietic necrosis virus (IHNV) is a severe disease that threats worldwide salmon and trout aquaculture, but there is currently no approved antiviral to treat the infection. In this study, tetrandrine, a key functional component of Chinese medicine, was screened and approved to inhibit IHNV (50 % inhibition concentration [IC50] = 0.3274 mu M) with minimal cytotoxicity. In vitro studies showed that tetrandrine dramatically inhibited diverse IHNV isolates on both the mRNA expression levels and viral titers, and in vivo studies showed that oral pre-treatment with 5 mg/kg tetrandrine could decrease IHNV loads and increase the survival rate of rainbow trout. The antiviral effect mainly occurred on RNA replication stage, during which the tetrandrine was predicted by using molecular docking to bind to the IHNV phosphoprotein (P protein) at the Asp-81 site, which involves interaction between P protein and polymerase protein (L protein). We introduced mutations to the Asp-81 region (including Asp-81, Lys-72, Lys-84, and Arg-94), and found that a single mutation to the Asp-81 could result in the failure of the rescue of recombinant IHNV mutants, which indicates that the Asp-81 plays a key role to start IHNV replication. So, the tetrandrine was likely to inhibit IHNV via binding to Asp-81 on the phosphoprotein of IHNV.

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