Novel anti-flavivirus drugs targeting the nucleolar distribution of core protein
Novel anti-flavivirus drugs targeting the nucleolar distribution of core protein
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针对核心蛋白核仁分布的新型抗黄病毒药物
DOI：
10.1016/j.virol.2019.11.015
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Matsuura Yoshiharu
中科院分区：
文献类型：
--
作者：
Tokunaga Makoto;Miyamoto Yoichi;Suzuki Tatsuya;Otani Mayumi;Inuki Shinsuke;Esaki Tsuyoshi;Nagao Chioko;Mizuguchi Kenji;Ohno Hiroaki;Yoneda Yoshihiro;Okamoto Toru;Oka Masahiro;Matsuura Yoshiharu
黄病毒引起的传染病的风险在全球范围内不断增加。在这里，我们开发了一种新的高通量筛选（HTS）系统，以评估靶向黄病毒核心蛋白核定位的化合物的抑制作用。我们筛选了4000化合物的基础上，他们的能力，抑制核定位的核心蛋白，并确定了超过20个化合物，包括抑制剂细胞周期蛋白依赖性激酶和糖原合成酶激酶。在基于细胞的感染系统中验证了所鉴定的化合物抑制病毒生长的功效。值得注意的是，核仁形态受到化合物处理的影响，表明核仁功能对病毒繁殖至关重要。本HTS系统通过靶向核心蛋白的核仁定位为鉴定抗黄病毒的抗病毒药提供了有用的策略。
The risk of infectious diseases caused byFlavivirusis 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.