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Establishment of a new therapeutic for the treatment of paramyxoviruses by using a mimic of viral genomic RNA.

Research Project

Project/Area Number 15K09672
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKurume University

Principal Investigator

Hara Koyu  久留米大学, 医学部, 准教授 (40309753)

Co-Investigator(Kenkyū-buntansha) 柏木 孝仁  久留米大学, 医学部, 講師 (70320158)
渡邊 浩  久留米大学, 医学部, 教授 (90295080)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsパラミクソウイルス / RSウイルス / 抗ウイルス薬 / RNAポリメラーゼ / RSV / ミニゲノム / P / ルシフェラーゼ / Pタンパク質 / Lタンパク質 / RNA複製酵素 / ミニゲノムアッセイ系 / 抗ウイルス作用 / 欠損変異型 / 非翻訳領域 / RNP
Outline of Final Research Achievements

Paramyxoviruses have a non-coding sequence (NCS) at both 5’-end and 3’-end of the genome. We assessed antiviral activities against paramyxoviruses by using interfering RNA that mimicked the NCS. However, its attempts were unsuccessful. Then, we evaluated whether peptides or small proteins derived from the ribonucleoprotein (P, L, N, M2-1) could be used as dominant negative inhibitors to inhibit viral replication. We found that the C-terminal 82 amino acids of P (P Fr) had a substantial anti-viral activity for respiratory syncytial virus (RSV). A pull-down experiment of P Fr showed that P Fr strongly interacts with full-length P and inhibits the viral RNA polymerase activity. Our results indicate that P Fr is a promising candidate for further development of antiviral drug for the treatment of paramyxoviruses, as well as RSV.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 4 results) Remarks (1 results)

  • [Int'l Joint Research] フランス国立農学研究所(フランス)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Basic amino acids in the N-terminal half of the PB2 subunit of influenza virus RNA polymerase are involved in both transcription and replication.2017

    • Author(s)
      Hara K, Kashiwagi T, Hamada N, and Watanabe H.
    • Journal Title

      J. Gen. Virol

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] マイクロRNAをかわすウイルスたち2016

    • Author(s)
      原 好勇
    • Journal Title

      久留米医学会雑誌

      Volume: 79 Pages: 1-7

    • Related Report
      2015 Research-status Report
  • [Journal Article] The N-terminal fragment of PA subunit of the influenza A virus effectively inhibits ribonucleoprotein (RNP) activity via supression of its RNP expression.2015

    • Author(s)
      Uemura Y, Kashiwagi T, Hara K, Nakazono Y, Hamada N, and Watanabe H.
    • Journal Title

      J Infect Chemother

      Volume: 21 Pages: 296-301

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] RSウイルスの増殖を抑制する欠損型Pの作用機序について2018

    • Author(s)
      八板謙一郎、原 好勇、柏木孝仁、渡邊 浩
    • Organizer
      第92回日本感染症学会総会・学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The C-terminal region of the respiratory syncytial virus phosphoprotein has an inhibitory effect on the polymerase activity.2017

    • Author(s)
      Yaita K, Hara K, Khamrin P, Kashiwagi T, Hamada N, and Watanabe H.
    • Organizer
      International Union of Microbiological Sciences 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RSウイルスの欠損型PはRSウイルスのポリメラーゼ活性を阻害する2017

    • Author(s)
      八板謙一郎、原 好勇、柏木孝仁、渡邊 浩
    • Organizer
      第87回日本感染症学会西日本地方会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] RSウイルスのPタンパク質C末端領域はウイルスRNPの合成を抑制する2017

    • Author(s)
      八板謙一郎, 原 好勇, 柏木孝仁, 濱田信之, 渡邊 浩
    • Organizer
      第91回日本感染症学会総会・学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The N-terminal fragments of the PB2 and PA subunits severely inhibit a ribonucleoprotein(RNP) activity of influenza A virus.2016

    • Author(s)
      Hara K
    • Organizer
      US/Japan Cooperative Medical Science Program
    • Place of Presentation
      Bethesda, USA
    • Year and Date
      2016-01-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新作用機序によるインフルエンザウイルス阻害剤への応用2016

    • Author(s)
      上村勇作、柏木孝仁、原 好勇、濱田信之、渡邊 浩
    • Organizer
      第86回日本感染症学会西日本地方会学術集会
    • Place of Presentation
      沖縄
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of amino acids critical for polymerase activity in the N-terminal region of the PB2 subunit of influenza virus RNA polymerase.2015

    • Author(s)
      Hara K, Kashiwagi T, Hamada N, and Watanabe H.
    • Organizer
      Negative Strand Virus Meeting
    • Place of Presentation
      Siena, Italy
    • Year and Date
      2015-06-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The N-terminal fragments of the PB2 and PA subunits severely inhibit a ribonucleoprotein (RNP) activity of influenza A virus.2015

    • Author(s)
      Uemura Y, Kashiwagi T, Hara K, Nakazono Y, Hamada N, and Watanabe H.
    • Organizer
      Negative Strand Virus Meeting
    • Place of Presentation
      Siena, Italy
    • Year and Date
      2015-06-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] インフルエンザウイルスRNAポリメラーゼPB2サブユニットのRNA結合部位の同定2015

    • Author(s)
      原 好勇、柏木孝仁、濱田信之、渡邊 浩
    • Organizer
      第89回日本感染症学会総会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report
  • [Presentation] ンフルエンザウイルスのN末端PAによるRNP合成阻害とその特異性について2015

    • Author(s)
      柏木孝仁、原 好勇、上村勇作、今村宜寛、濱田信之、渡邊 浩
    • Organizer
      第89回日本感染症学会総会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report
  • [Remarks] 久留米大学医学部感染制御学講座

    • URL

      http://www.med.kurume-u.ac.jp/med/virol/jp/index.html

    • Related Report
      2016 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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