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2015 Fiscal Year Final Research Report

Screening of inhibitors against influenza A virus PA endonuclease

Research Project

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Project/Area Number 25460574
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionTokushima Bunri University

Principal Investigator

Kuzuhara Takashi  徳島文理大学, 薬学部, 教授 (00260513)

Project Period (FY) 2013-04-01 – 2016-03-31
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 / PA / フラーレン / 漢方
Outline of Final Research Achievements

To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro influenza A RNA polymerase PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs.
Furthermore, the Kampo medicines kakkonto, shosaikoto, saikokeishito, keishito, maobushisaishinto, and maoto, but not chikujountanto, inhibited PA endonuclease activity in a dose-dependent manner. Our results indicate that Kampo medicines are good sources providing a structural lead for optimization of an influenza endonuclease inhibitor.

Free Research Field

生化学

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Published: 2017-05-10  

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