The risk of infectious diseases caused by Flavivirus is increasing globally. Here, we developed a novel high-throughput screening (HTS) system to evaluate the inhibitory effects of compounds targeting the nuclear localization of the flavivirus core protein. We screened 4000 compounds based on their ability to inhibit the nuclear localization of the core protein, and identified over 20 compounds including inhibitors for cyclin dependent kinase and glycogen synthase kinase. The efficacy of the identified compounds to suppress viral growth was validated in a cell-based infection system. Remarkably, the nucleolus morphology was affected by the treatment with the compounds, suggesting that the nucleolus function is critical for viral propagation. The present HTS system provides a useful strategy for the identification of antivirals against flavivirus by targeting the nucleolar localization of the core protein.

中文翻译：

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针对核心蛋白核仁分布的新型抗黄病毒药物。

全球范围内，由黄病毒引起的传染病风险正在增加。在这里，我们开发了一种新型的高通量筛选（HTS）系统，以评估针对黄病毒核心蛋白核定位的化合物的抑制作用。我们基于抑制核心蛋白核定位的能力筛选了4000种化合物，并鉴定了20多种化合物，包括细胞周期蛋白依赖性激酶和糖原合酶激酶的抑制剂。鉴定出的化合物抑制病毒生长的功效已在基于细胞的感染系统中得到验证。值得注意的是，核仁形态受到化合物处理的影响，表明核仁功能对于病毒繁殖至关重要。