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Influenza viral hemagglutinin-targeted macrocyclic peptides as an antiviral agent

Research Project

Project/Area Number 25670224
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Virology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KOHARA Michinori  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 特任研究員 (10250218)

Co-Investigator(Renkei-kenkyūsha) YASUI Fumihiko  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (40399473)
MUNAKATA Tubasa  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (50420237)
SAITO Makoto  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (20433021)
MUNEKATA Keisuke  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (30569140)
SUGA Hiroaki  東京大学, 大学院理学系研究科, 教授 (00361668)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsインフルエンザ / 特殊環状ペプチド / 感染阻害 / インフルエンザウイルス / HA蛋白質 / 抗ウイルス剤 / パントロピック / 増殖阻害
Outline of Final Research Achievements

To devise smaller molecules capable of binding to the influenza viral HA and have the potential as an antiviral agent, we used an emerging technology, RaPID (Random non-standard Peptide Integrated Discovery) system. After five rounds selection of H5N1 HA-binding peptides, we found a total of 24 candidates for inhibitor HA (iHA).
iHA inhibited plaque formation against different clade H5N1 viruses, A/whooper swan/Mongolia/3/05 (H5N1/Mongolia; clade 2.2) and A/whooper swan/Hokkaido/1/08 (H5N1/Hokkaido; clade 2.3). Intriguingly, iHA was effective against pandemic (H1N1) 2009 viruses more than zanamivir. These results suggest that iHA is able to inhibit replication of a wide range of H1 and H5 influenza viruses via a mechanism of its interaction with HA. Polykaryon formation mediated by various clade H5 HAs were also inhibited by iHA in a dose-dependent manner.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (13 results)

All 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus.2014

    • Author(s)
      Yasui F, Kohara M, Kitabatake M, Nishiwaki T, Fujii H, Tateno C, Yoneda M, Morita K, Matsushima K, Koyasu S, Kai C
    • Journal Title

      Virology

      Volume: 454-455 Pages: 157-168

    • DOI

      10.1016/j.virol.2014.02.005

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tupaia belangeri as an experimental animal model for viral infection2014

    • Author(s)
      Kyoko Tsukiyama-Kohara, Michinori Kohara
    • Journal Title

      Experimental Animals

      Volume: 63 Pages: 367-374

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus2013

    • Author(s)
      Ogiwara H, Yasui F, Munekata K, Takagi-Kamiya A, Munakata T, Nomura N, Shibasaki F, Kuwahara K, Sakaguchi N, Sakoda Y, Kida H, Kohara M
    • Journal Title

      Am. J. Pathol

      Volume: 184 Issue: 1 Pages: 171-183

    • DOI

      10.1016/j.ajpath.2013.10.004

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Broad-spectrum detection of h5 subtype influenza a viruses with a new fluorescent immunochromatography system2013

    • Author(s)
      Sakurai A, Takayama K, Nomura N, Munakata T, Yamamoto N, Tamura T, Yamada J, Hashimoto M, Kuwahara K, Sakoda Y, Suda Y, Kobayashi Y, Sakaguchi N, Kida H, Kohara M, Shibasaki F
    • Journal Title

      PLoS One

      Volume: 8 Issue: 11 Pages: e76753-e76753

    • DOI

      10.1371/journal.pone.0076753

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Experimental Infection of Macaques with a Wild Water Bird-Derived Highly Pathogenic Avian Influenza Virus (H5N1).2013

    • Author(s)
      Fujiyuki, T., Yoneda, M., Yasui, F., Kuraishi, T., Hattori, S., Kwon, HJ., Munekata, K., Kiso, Y., Kida, H., Kohara, M., Kai, C.
    • Journal Title

      PLoS One

      Volume: 18;8(12) Issue: 12 Pages: e83551-e83551

    • DOI

      10.1371/journal.pone.0083551

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Highly pathogenic avian influenza A H5N1 virus causes severe symptoms due to insufficient induction of humoral immune response2014

    • Author(s)
      Ai Ikejiri, Fumihiko Yasui, Yasushi Itoh, Masahiro Kitabatake, Nobuo Sakaguchi, Kazumasa Ogasawara, Michinori Kohara
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] H5N1高病原性鳥インフルエンザウイルス感染に対する哺乳動物宿主の免疫応答とインフルエンザ組換え生ワクチン接種による発症防御2014

    • Author(s)
      安井文彦、伊藤 靖、池尻 藍、北畠正大、宗方圭祐、迫田義博、喜田 宏、坂口薫雄、小笠原一誠、小原道法
    • Organizer
      第18回日本ワクチン学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2014-12-06 – 2014-12-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] H5N1高病原性鳥インフルエンザ組換えワクシニアワクチン単回接種による免疫長期持続作用機序の解析2014

    • Author(s)
      安井文彦、宗方圭祐、倉石 武、服部正策、藤幸知子、米田美佐子、迫田義博、喜田 宏、甲斐智恵子、小原道法
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 亜型を超えた感染阻害活性を示すヘマグルチニン結合性特殊環状ペプチド2014

    • Author(s)
      斉藤 誠、安井文彦、棟方 翼、飛田良美、小澤 真、小原恭子、伊東利紗、菅 裕明、佐々木 亨、窪田規一、小原道法
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Prophylatic effect of H5N1 influenza vaccine based on vaccinia virus vector in cynomolgus monkeys2014

    • Author(s)
      Fumihiko Yasui, Keisuke Munekata, Yasushi Itoh, Tomoko Fujiyuki, Takeshi Kuraishi, Yoshihiro Sakoda, Misako Yoneda, Hiroshi Kida, Shosaku Hattori, Chieko Kai, Kazumasa Ogasawara, Michinori Kohara
    • Organizer
      8th Vaccine & ISV Congress
    • Place of Presentation
      Philadelphia (USA)
    • Year and Date
      2014-10-26 – 2014-10-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Prophylatic effect of H5N1 influenza vaccine based on attenuated replicative vaccinia virus that contains endogenous adjuvant component2014

    • Author(s)
      Fumihiko Yasui, Keisuke Munekata, Yasushi Itoh, Tomoko Fujiyuki, Takeshi Kuraishi, Yoshihiro Sakoda, Misako Yoneda, Hiroshi Kida, Shosaku Hattori, Chieko Kai, Kazumasa Ogasawara, Michinori Kohara
    • Organizer
      KeystoneSymposia
    • Place of Presentation
      Seattle (USA)
    • Year and Date
      2014-10-08 – 2014-10-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 霊長類感染モデルを用いた高病原性鳥インフルエンザウイルス抗原発現組換え麻疹ウイルスの防御効果の解析2014

    • Author(s)
      藤幸知子、堀江 亮、米田美佐子、倉石 武、安井文彦、宗片圭祐、池田房子、基礎友里、権賢 貞、石井美穂、佐藤宏樹、服部正策、喜田 宏、小原道法、甲斐知恵
    • Organizer
      第61回日本実験動物学会
    • Place of Presentation
      札幌コンベンションセンター(札幌)
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Remarks] 公益財団法人東京都医学総合研究所プロジェクト研究

    • URL

      http://www.igakuken.or.jp/project/detail/infectious.html

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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