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synergistic effects of functional constituents in food and antiviral drug: is it possible to overcome drug-resistance and to prevent flu?

Research Project

Project/Area Number 16K00853
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Eating habits
Research InstitutionYasuda Women's University (2019)
Nagasaki University (2016-2018)

Principal Investigator

WATANABE Ken  安田女子大学, 家政学部, 准教授 (00346909)

Project Period (FY) 2016-04-01 – 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 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsインフルエンザウイルス / 機能性食品 / 薬剤耐性 / インフルエンザ / 相乗効果 / 食品 / 機能成分 / 抗ウイルス活性 / 落花生 / 抗ウイルス / in vitro / 抗ウイルス効果
Outline of Final Research Achievements

Communicable diseases caused by virus infection are threat to humans. There are many antivirals, however, viruses acquire drug resistance easily. I focused on flu, caused by influenza virus infection. To overcome this issue, I found chemical constituents in food that suppress influenza virus replication. Also, I found that chemical compounds that have novel mechanisms of action. By using these chemicals, I successfully found that synergistic effects when these compounds were used with currently used antivirals, such as Oseltamivir. Combination use of compounds that have different mechanisms of action is useful strategy to prevent acquisition of drug resistance.

Academic Significance and Societal Importance of the Research Achievements

研究成果では、第一にこれまでにない作用機序をもつ抗インフルエンザウイルス薬開発を行った事である。国内特許およびPCT出願まで行った、インフルエンザウイルスポリメラーゼ蛋白質間の結合を阻害する化合物の開発に成功した。第二に食品の機能成分として落花生薄皮抽出液中のポリフェノール類が抗ウイルス活性をもつことを初めて明らかにしたものであり、これらの成果は今後のインフルエンザパンデミックに備えた基礎研究となることが期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2020 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (15 results) (of which Int'l Joint Research: 5 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] A Quinolinone Compound Inhibiting the Oligomerization of Nucleoprotein of Influenza A Virus Prevents the Selection of Escape Mutants2020

    • Author(s)
      Makau Juliann Nzembi, Watanabe Ken, Otaki Hiroki, Mizuta Satoshi, Ishikawa Takeshi, Kamatari Yuji O., Nishida Noriyuki
    • Journal Title

      Viruses

      Volume: 12 Issue: 3 Pages: 337-337

    • DOI

      10.3390/v12030337

    • NAID

      120006988247

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antiviral Activity of Peanut (Arachis hypogaea L.) Skin Extract Against Human Influenza Viruses2018

    • Author(s)
      Makau Juliann Nzembi、Watanabe Ken、Mohammed Magdy M.D.、Nishida Noriyuki
    • Journal Title

      Journal of Medicinal Food

      Volume: 21 Issue: 8 Pages: 777-784

    • DOI

      10.1089/jmf.2017.4121

    • NAID

      120006987956

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Drug-Repositioning Approach for the Discovery of Anti-Influenza Virus Activity of Japanese Herbal (Kampo) Medicines In Vitro: Potent High Activity of Daio-Kanzo-To2018

    • Author(s)
      Watanabe Ken
    • Journal Title

      Evidence-Based Complementary and Alternative Medicine

      Volume: 2018 Issue: 1 Pages: 1-9

    • DOI

      10.1155/2018/6058181

    • NAID

      120006987872

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of Trifluoromethyl-α,β-unsaturated Lactones and Pyrazolinones and Discovery of Influenza Virus Polymerase Inhibitors2018

    • Author(s)
      Mizuta Satoshi、Makau Juliann Nzembi、Kitagawa Ayako、Kitamura Kanami、Otaki Hiroki、Nishi Kodai、Watanabe Ken
    • Journal Title

      ChemMedChem

      Volume: 13 Issue: 22 Pages: 2390-2399

    • DOI

      10.1002/cmdc.201800511

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure-based drug discovery for combating influenza virus by targeting the PA?PB1 interaction2017

    • Author(s)
      Watanabe Ken、Ishikawa Takeshi、Otaki Hiroki、Mizuta Satoshi、Hamada Tsuyoshi、Nakagaki Takehiro、Ishibashi Daisuke、Urata Shuzo、Yasuda Jiro、Tanaka Yoshimasa、Nishida Noriyuki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 9500-9500

    • DOI

      10.1038/s41598-017-10021-w

    • NAID

      120006987424

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of Small Molecule Inhibitors for Influenza A Virus Using In Silico and In Vitro Approaches,2017

    • Author(s)
      Makau JN, Watanabe K, Ishikawa T, Mizuta S, Hamada T, Kobayashi N, Nishida N
    • Journal Title

      PLoS ONE

      Volume: 12 Issue: 3 Pages: e0173582-e0173582

    • DOI

      10.1371/journal.pone.0173582

    • NAID

      120006987539

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] インフルエンザRNAポリメラーゼPA-PB1蛋白質間相互作用阻害剤の開発研究2020

    • Author(s)
      水田 賢志、大滝 大樹、渡邊 健
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 計算化学を利用した薬剤耐性変異予測法の開発とオセルタミビル耐性インフルエンザウイルスでの検証2019

    • Author(s)
      石川岳志、大滝大樹、Juliann Nzembi Makau、渡邊健、水田賢志、鎌足雄司、田中義正、西田教行
    • Organizer
      第56回日本ウイルス学会九州支部総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Antiviral activity of bean extract against human influenza virus2019

    • Author(s)
      Juliann Nzembi Makau, Ken Watanabe, Satoshi Mizuta, Noriyuki Nishida
    • Organizer
      The 18th International Forum on Infection and Immunity
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インフルエンザウイルス複製を標的とした蛋白質-蛋白質相互作用阻害剤の開発2018

    • Author(s)
      渡邊健、Juliann Nzembi Makau、石川岳志、大滝大樹、水田賢志、中垣岳大、石橋大輔、浦田秀造、安田二朗、西田教行
    • Organizer
      第55回 日本ウイルス学会九州支部総会・第71回 日本細菌学会九州支部総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Identification of influenza A virus inhibitors targeting viral nucleoprotein.2018

    • Author(s)
      Juliann Nzembi Makau, Ken Watanabe, Takeshi Ishikawa, Satoshi Mizuta, Nobuyuki Kobayashi, Noriyuki Nishida
    • Organizer
      第55回 日本ウイルス学会九州支部総会・第71回 日本細菌学会九州支部総会
    • Related Report
      2018 Research-status Report
  • [Presentation] インフルエンザウイルスポリメラーゼ複合体を標的とした抗ウイルス薬の開発2018

    • Author(s)
      渡邊健、Juliann Nzembi Makau1, 水田賢志
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ピーナッツ薄皮抽出液の抗インフルエンザウイルス活性2018

    • Author(s)
      渡邊健、Juliann Nzembi Makau, 田島民雄、西田教行
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規作用機序をもつ抗インフルエンザウイルス薬の開発2018

    • Author(s)
      渡邊 健、石川岳志、大滝大樹、水田賢志、濱田剛、浦田秀造、安田二朗、田中義正、西田教行
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新たな作用機序をもつ抗インフルエンザウイルス薬の開発2017

    • Author(s)
      渡辺健、石川岳志、水田賢志、中垣岳大、大滝大樹、濱田剛、田中義正、西田教行
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学(宮城県仙台市)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
  • [Presentation] Targeting viral nucleoprotein in search for new influenza A virus inhibitors.2017

    • Author(s)
      Juliann Nzembi Makau, Ken Watanabe, Takeshi Ishikawa, Satoshi Mizuta, Tsuyoshi Hamada, Nobuyuki Kobayashi, Noriyuki Nishida.
    • Organizer
      The 13th Nagasaki-Singapore Medical Symposium / Leading Program International Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structure-based discovery of inhibitors targeting influenza A virus nucleoprotein.2017

    • Author(s)
      Juliann Nzembi Makau, Ken Watanabe, Takeshi Ishikawa, Satoshi Mizuta, Tsuyoshi Hamada, Nobuyuki Kobayashi, Noriyuki Nishida.
    • Organizer
      17th International congress of virology (ICV)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規作用機序をもつ抗インフルエンザ薬の開発2017

    • Author(s)
      渡邊 健
    • Organizer
      第5回TR推進合同フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] Drug discovery for influenza virus using in silico and in vitro approaches2016

    • Author(s)
      3.Juliann Nzembi Makau, Ken Watanabe, Takeshi Ishikawa, Satoshi Mizuta, Tsuyoshi Hamada, Nobuyuki Kobayashi, Noriyuki Nishida
    • Organizer
      The 15th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県淡路市)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Discovery of influenza virus inhibitors using in silico and in vitro approaches2016

    • Author(s)
      2.Juliann Nzembi Makau, Ken Watanabe, Takeshi Ishikawa, Tsuyoshi Hamada, Nobuyuki Kobayashi, Noriyuki Nishida
    • Organizer
      第5回感染症若手フォーラム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県淡路市)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Research-status Report
  • [Presentation] Drug discovery for influenza virus2016

    • Author(s)
      4.Juliann Nzembi Makau, Ken Watanabe, Takeshi Ishikawa, Tsuyoshi Hamada, Nobuyuki Kobayashi, Noriyuki Nishida
    • Organizer
      The 3rd International Symposium for the Promotion of Science and Technology Innovation Cooperation between Africa and Japan
    • Place of Presentation
      JICA市ヶ谷ビル(東京都新宿区)
    • Year and Date
      2016-07-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] キノリノン化合物および抗RNAウイルス薬2018

    • Inventor(s)
      水田賢志,渡邊健,西田教行,濱田剛,石川岳志 他4名
    • Industrial Property Rights Holder
      国立大学法人長崎大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] キノリノン化合物および抗RNAウイルス治療薬2017

    • Inventor(s)
      水田賢志、渡邊健、西田教行、濱田剛、石川岳志、田中義正、大滝大樹
    • Industrial Property Rights Holder
      長崎大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-072230
    • Filing Date
      2017-03-31
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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