WEKO3
アイテム
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An Antiviral Drug Screening Platform with a FRET Biosensor for Measurement of Arenavirus Z Assembly
http://hdl.handle.net/10069/00040476
http://hdl.handle.net/10069/000404768e2b24db-37ee-409c-975b-0b13fed9764d
名前 / ファイル | ライセンス | アクション |
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CSF45_155.pdf (485.6 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-01-22 | |||||
タイトル | ||||||
タイトル | An Antiviral Drug Screening Platform with a FRET Biosensor for Measurement of Arenavirus Z Assembly | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Anti-viral drugs | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Arenavirus | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Förster resonance energy transfer | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Z protein | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Mizutani, Tatsuaki
× Mizutani, Tatsuaki× Ohba, Yusuke× Mizuta, Satoshi× Yasuda, Jiro× Urata, Shuzo |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The smallest arenavirus gene product, Z protein, plays critical roles in the virus life cycle. Z is the major driving force of budding and particle production because of a unique property that defines self-assembly. In addition to the roles in budding, Z also participates in the suppression of type I interferon production to evade host antiviral immunity. Therefore, Z and its assembled form are an attractive drug target for arenaviral hemorrhagic fever, such as Lassa fever. Here, we developed a biosensor that enabled the evaluation of the prototype arenavirus, lymphocytic choriomeningitis virus (LCMV), Z assembly using the principle of Förster resonance energy transfer (FRET). This FRET biosensor consisted of three tandem Z that were sandwiched between super-enhanced cyan-emitting fluorescent protein and variant of a yellow-emitting mutant of green fluorescent protein so that Z-Z intermolecular binding via the really interesting new gene finger domain increased the emission ratio. To identify novel anti-arenavirus compounds, the FRET biosensor was employed to screen the PathogenBox400 for inhibitors of Z assembly in a 96-well plate format. The assay performed well, with a Z’-factor of 0.89, and identified two compounds that decreased the emission ratio of the FRET biosensor in a dose-dependent manner. Of them, the compound, 5,6,7,8-tetrahydro-7-(benzyl)-pyrido[4',3':4,5]thieno[2,3-d] pyrimidin-2,4-diamine, was found to significantly inhibit LCMV propagation in infected cells. Thereby, the present study demonstrated that a novel FRET biosensor incorporating Z assembly built on FRET and named Zabton, was a valuable screening tool to identify anti-arenavirus compounds in the context of inhibition of Z assembly. | |||||
書誌情報 |
Cell Structure and Function 巻 45, 号 2, p. 155-163, 発行日 2020-12-25 |
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出版者 | ||||||
出版者 | 日本細胞生物学会 | |||||
出版者別言語 | ||||||
Japan Society for Cell Biology | ||||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0386-7196 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1247/csf.20030 | |||||
権利 | ||||||
権利情報 | ©2020 The Author(s). This is an open access article distributed under the terms of the Creative Commons BY (Attribution) License (https://creativecommons.org/licenses/by/4.0/legalcode), which permits the unrestricted distribution, reproduction and use of the article provided the original source and authors are credited. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Cell Structure and Function, 45(2), pp.155-163; 2020 |