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Novel therapeutic strategy for influenza and control of apoptosis of virus-infected cells

Research Project

Project/Area Number 17K10119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionFukushima Medical University

Principal Investigator

Sato Masatoki  福島県立医科大学, 医学部, 講師 (60423795)

Co-Investigator(Kenkyū-buntansha) 橋本 浩一  福島県立医科大学, 医学部, 准教授 (50322342)
細矢 光亮  福島県立医科大学, 医学部, 教授 (80192318)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsインフルエンザ / ノイラミニダーゼ阻害薬 / プロテアーゼ阻害薬 / インフルエンザウイルス / ノイラミニゼー阻害薬 / ウイルス / 感染症
Outline of Final Research Achievements

We examined therapeutic strategies for patients who develop severe influenza caused by influenza A virus variant with reduced susceptibility to oseltamivir and peramivir. Even if a cell is infected with this variant and cultured in a culture medium containing oseltamivir or peramivir, a high concentration of a drug is required to inhibit sufficiently the growth of the virus. However, it was found that by adding a protease inhibitor, Camostat mesilate and Nafamostat Mesilate, here, the virus growth can be inhibited even with relatively low concentrations of oseltamivir or peramivir. It was also confirmed that the concentration of each drug used at that time was not toxic to cells.

Academic Significance and Societal Importance of the Research Achievements

本研究により、オセルタミビルもしくはペラミビルに感受性が低下したインフルエンザウイルス(以下変異ウイルス)に感染し重症化した患者さんに対しては、これら既存の抗インフルエンザ薬に加え、カモスタットやナファモスタットといったプロテアーゼ阻害薬を併用することで、治療が可能である可能性が示されました。特に静注薬であるペラミビルとナファモスタットを併用すると、それぞれ単独での有効濃度よりも低い濃度でウイルス増殖を抑制できることが判明しました。
これまで変異ウイルスによる重症例に対しては有効な抗ウイルス療法はありませんでしたが、作用機序の異なる薬剤を併用することで、治療が可能であることが示されました。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Immune response after a single intravenous peramivir administration in children with influenza2018

    • Author(s)
      Masatoki Sato, Koichi Hashimoto, Yukihiko Kawasaki, Mitsuaki Hosoya
    • Journal Title

      Antiviral Therapy

      Volume: in press Issue: 5 Pages: 435-441

    • DOI

      10.3851/imp3222

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Presentation] バロキサビルの臨床的・ウイルス学的効果の検討2019

    • Author(s)
      佐藤 晶論、高下 恵美、片寄 雅彦、根本 健二、酒井 信子、橋本 浩一、細矢 光亮1
    • Organizer
      第51回日本小児感染症学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Clinical and virological efficacy of baloxavir marboxil in children with influenza A2019

    • Author(s)
      Masatoki Sato, Emi Takashita, Masahiko Katayose, Kenji Nemoto, Nobuko Sakai Koichi Hashimoto, Mitsuaki Hosoya
    • Organizer
      Options X for the Control of Influenza
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synergistic effect of nafamostat mesilate and neuraminidase inhibitors against the H1N1 pdm09 H275Y variant2017

    • Author(s)
      Masatoki Sato , Koichi Hashimoto , Mitsuaki Hosoya
    • Organizer
      The 6th ESWI Influenza Conference,
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] プロテアーゼ阻害薬とノイラミニダーゼ阻害薬併用によるインフルエンザ治療戦略の基礎的検討2017

    • Author(s)
      佐藤 晶論 橋本 浩一 細矢 光亮
    • Organizer
      第49回日本小児感染症学会総会・学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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