Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore.
Antiviral Res. 2013 Sep;99(3):301-6. doi: 10.1016/j.antiviral.2013.06.002. Epub 2013 Jun 14.
Infection by one of the 4 distinct serotypes of dengue virus (DENV) threatens >40% of the world's population, with no efficacious vaccine or antiviral agent currently available. DENV replication through the virus-encoded nonstructural protein (NS) 5 protein occurs in the infected cell cytoplasm, but NS5 from DENV2 has thus far been shown to localize strongly in the nucleus throughout infection. Here we use specific antibodies cross-reactive with NS5 from DENV1-4 to demonstrate nuclear localization of NS5 from all DENV serotypes for the first time in both infected as well as transfected cells, although to differing extents. The small-molecule inhibitor Ivermectin was inhibitory towards both DENV 1 and 2 NS5 interaction with its nuclear transporter importin α/β in vitro, and protected against infection from DENV1-4. Ivermectin thus has potential in the clinical setting as a dengue antiviral.
登革热病毒（DENV）的 4 种不同血清型之一的感染威胁着全球超过 40%的人口，但目前尚无有效的疫苗或抗病毒药物。DENV 通过病毒编码的非结构蛋白（NS）5 蛋白在感染细胞的细胞质中复制，但迄今为止，DENV2 的 NS5 已被证明在整个感染过程中强烈定位于细胞核中。在这里，我们使用与 DENV1-4 的 NS5 交叉反应的特异性抗体，首次在感染和转染的细胞中证明了所有 DENV 血清型的 NS5 的核定位，尽管程度不同。小分子抑制剂伊维菌素在体外抑制 DENV1 和 2 NS5 与核转运蛋白 importin α/β 的相互作用，并能预防 DENV1-4 的感染。因此，伊维菌素在临床上有作为抗登革热病毒的潜力。
