2013 Fiscal Year Final Research Report
Identification of a novel inhibitor of influenza virus polymerase based on inhibition of conformational change required for cap-dependent endonuclease activity
| Project/Area Number |
24659139
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Microbial Chemistry Research Foundation |
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Principal Investigator |
YAMASAKI Manabu 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (50442570)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKIZAWA Naoki 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (50448502)
MIZUMOTO Kiyohisa 公益財団法人微生物化学研究会, 微生物化学研究所, 研究アドバイザー (80092344)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | インフルエンザウイルス / RNAポリメラーゼ / エンドヌクレアーゼ / キャップ構造 / 質量分析フットプリント法 / 抗ウイルス薬 |
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| Research Abstract |
Influenza viral polymerase cleaves capped RNA fragments from cellular mRNAs and uses as primers for initiating viral transcription, which generates capped viral mRNA molecules. This unique mechanism is a target for the discovery of anti-influenza therapeutics. In this study, we investigated a conformational change of this enzyme required for the endonuclease activity, and screened enzymatic inhibitor based on inhibition of the identified conformational change. We identified the protein region showing the conformational change upon cap-binding and two small compounds as an inhibitor of both this change and cap-dependent endonuclease activity.
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Research Products
(4 results)
