Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus.
Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus.
复制标题
伊维菌素是进口蛋白α/β介导的核进口的特异性抑制剂，能够抑制HIV-1和登革热病毒的复制。
DOI：
10.1042/bj20120150
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发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Jans DA
中科院分区：
文献类型：
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作者：
Wagstaff KM;Sivakumaran H;Heaton SM;Harrich D;Jans DA
由蛋白质的importin超家族介导的蛋白质在细胞质和细胞核之间的移动对于许多细胞过程（包括分化和发育）是必不可少的，并且对于疾病状态（诸如病毒性疾病和肿瘤发生）是关键的。我们最近开发了一种高通量筛选方法来鉴定蛋白质核输入的特异性和一般性抑制剂，其中伊维菌素被鉴定为输入素α/β介导的转运的潜在抑制剂。在本研究中，我们详细描述了伊维菌素的核转运抑制特性，证明它是importin α/β核输入的广谱抑制剂，对一系列其他核输入途径没有影响，包括单独由importin β1介导的核输入途径。重要的是，我们首次确定伊维菌素对HIV-1和登革病毒都具有强效抗病毒活性，这两种病毒分别与HIV-1整合酶和NS 5（非结构蛋白5）聚合酶蛋白密切依赖于输入素α/β核输入。伊维菌素似乎是研究蛋白质核输入的宝贵工具，也是未来开发抗病毒药物的基础。
The movement of proteins between the cytoplasm and nucleus mediated by the importin superfamily of proteins is essential to many cellular processes, including differentiation and development, and is critical to disease states such as viral disease and oncogenesis. We recently developed a high-throughput screen to identify specific and general inhibitors of protein nuclear import, from which ivermectin was identified as a potential inhibitor of importin α/β-mediated transport. In the present study, we characterized in detail the nuclear transport inhibitory properties of ivermectin, demonstrating that it is a broad-spectrum inhibitor of importin α/β nuclear import, with no effect on a range of other nuclear import pathways, including that mediated by importin β1 alone. Importantly, we establish for the first time that ivermectin has potent antiviral activity towards both HIV-1 and dengue virus, both of which are strongly reliant on importin α/β nuclear import, with respect to the HIV-1 integrase and NS5 (non-structural protein 5) polymerase proteins respectively. Ivermectin would appear to be an invaluable tool for the study of protein nuclear import, as well as the basis for future development of antiviral agents.