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Study of the molecular mechanisms of novel therapeutic candidate for cytomegalovirus infection

Research Project

Project/Area Number 15K09587
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionHokuriku University

Principal Investigator

MURAYAMA Tsugiya  北陸大学, 薬学部, 研究員 (60159184)

Co-Investigator(Kenkyū-buntansha) 定成 秀貴  北陸大学, 薬学部, 講師 (60121274)
Co-Investigator(Renkei-kenkyūsha) EIZURU Yoshito  鹿児島大学, 医学部, 名誉教授 (00041351)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsヒトサイトメガロウイルス / トリシン / ケモカイン / 抗ウイルス薬 / 抗HCMV薬 / CCL2 / CCL5
Outline of Final Research Achievements

As a result of examining the molecular action mechanism of a novel therapeutic candidate "tricin" against human cytomegalovirus (HCMV), it was revealed that the action mechanism through the host chemokines molecule exists (Antiviral Res. 148, 15-19). In addition, from the study of the molecular mechanism of tricin suppression of HCMV gene expression, tricin inhibits the activity of RNA pol II by inhibiting the kinase activity of CDK9, and as a result, the molecular mechanism that suppresses the transcriptional activity of HCMV gene is obvious (FEBS Open Bio. 8, 646-654). Furthermore, by searching for a compound having more potent anti-HCMV activity than tricin, a compound having about 400 times more potent activity than tricin was synthesized by adding fluorine to tricin (Antiviral Res. 154, 10-16).

Report

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

    (36 results)

All 2018 2017 2016 2015

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] The anti-human cytomegalovirus drug tricin inhibits cyclin-dependent kinase 92018

    • Author(s)
      Hidetaka Sadanari, Kazuhiro J. Fujimoto, Yuto Sugihara, Tomoki Ishida, Masaya Takemoto, Tohru Daikoku, Tsugiya Murayama
    • Journal Title

      FEBS Open Bio

      Volume: 8 Issue: 4 Pages: 646-654

    • DOI

      10.1002/2211-5463.12398

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An in silico-designed flavone derivative, 6-fluoro-4′-hydroxy-3′,5′-dimethoxyflavone, has a greater anti-human cytomegalovirus effect than ganciclovir in infected cells2018

    • Author(s)
      Kazuhiro J. Fujimoto, Daiki Nema, Masayuki Ninomiya, Mamoru Koketsu, Hidetaka Sadanari, Masaya Takemoto, Tohru Daikoku, Tsugiya Murayama
    • Journal Title

      Antivir. Res.

      Volume: 154 Pages: 10-16

    • DOI

      10.1016/j.antiviral.2018.03.006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of human cytomegalovirus replication by tricin is associated with depressed CCL2 expression2017

    • Author(s)
      Yumiko Akai, Hidetaka Sadanari, MasayaTakemoto, Noboru Uchide, Tohru Daikoku, Naofumi Mukaida, Tsugiya Murayama
    • Journal Title

      Antiviral Research

      Volume: 148 Pages: 15-19

    • DOI

      10.1016/j.antiviral.2017.09.018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCL2/CCR2-dependent replication of human cytomegalovirus is inhibited by anti-inflammatory compound tricin.2017

    • Author(s)
      Tsugiya Murayama, Daiki Nema, Hidetaka Sadanari, Masaya Takemoto, Tohru Daikoku, Naofumi Mukaida
    • Journal Title

      Cytokines (Special Issue)

      Volume: 100 Pages: 80-80

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] クマザサ含有成分によるCCL2依存性のヒトサイトメガロウイルス増殖抑制効果2017

    • Author(s)
      赤井佑三子、茂木香保里、定成秀貴、武本眞清、松原京子、大黒 徹、土田裕三、桜井大輔、村山次哉
    • Journal Title

      日本補完代替医療学会誌

      Volume: 14 Pages: 83-93

    • NAID

      130006147572

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of CCL2 dependent human cytomegalovirus replication by tricin.2016

    • Author(s)
      Tsugiya Murayama, Rie Yamada, Keiko Matsubara, Hidetaka Sadanari
    • Journal Title

      F1000 Research

      Volume: 5 Pages: 561-561

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of matrix metalloproteinases-2 and -9 gene expression in cultured human fetal membrane cells by influenza virus infection.2016

    • Author(s)
      Noboru Uchide, Kyoko Obatake, Rie Yamada, Hidetaka Sadanari, Keiko Matsubara, Tsugiya Murayama, Kunio Ohyam
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 39 Pages: 1912-1921

    • NAID

      130005171512

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synergistic effects of combination treatment with ganciclovir and tricin on human cytomegalovirus replication in vitro. Antiviral Research.2016

    • Author(s)
      Rie Yamada, Hideki Suda, Hidetaka Sadanari, Keiko Matsubara, Yuuzo Tuchida, Tsugiya Murayama
    • Journal Title

      Antiviral Research

      Volume: 125 Pages: 79-83

    • DOI

      10.1016/j.antiviral.2015.11.008

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] イネ科植物含有成分“Tricin”による抗ヒトサイトメガロウイルス作用機序の解明2015

    • Author(s)
      村山次哉
    • Journal Title

      New Food Industry

      Volume: 57 Pages: 24-34

    • NAID

      40020470504

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] The novel compound shows potent anti-human cytomegalovirus activity2018

    • Author(s)
      Tsugiya Murayama, Kazuhiro J. Fujimoto, Mamoru Koketsu, Masayuki Ninomiya, Hidetaka Sadanari, Masaya Takemoto, Tohru Daitoku
    • Organizer
      5th International Congress on Technology, Engineering & Science
    • Related Report
      2017 Annual Research Report
  • [Presentation] CCL5-dependent replication of human cytomegalovirus is inhibited by tricin in vitro.2018

    • Author(s)
      T. Murayama, H. Sadanari, M. Takemoto, T. Daikoku
    • Organizer
      18th International Congress on Infectious Diseases
    • Related Report
      2017 Annual Research Report
  • [Presentation] 超強力な抗ヒトサイトメガロウイルス活性を有する新規化合物について2018

    • Author(s)
      根間大貴、藤本和宏、纐纈 守、二ノ宮真之、定成秀貴、武本眞清、大黒 徹、村山次哉
    • Organizer
      日本薬学会第138回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗ヒトサイトメガロウイルス活性のあるtricinがRNA polymerase II C-terminal domeinのリン酸化を阻害する2018

    • Author(s)
      定成秀貴、杉原雄斗、藤本和宏、武本眞清、大黒 徹、村山次哉
    • Organizer
      日本薬学会第138回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Inhibition of host factor-dependent human cytomegalovirus replication by tricin2017

    • Author(s)
      Tsugiya Murayama, Hidetaka Sadanari, Masaya Takemoto, Keiko Matsubara, Tohru Daikoku;
    • Organizer
      2nd World Congress & Expo on Pharmaceutics & Drug Delivery Systems (Pharmaceutics- 2017)
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 日和見ウイルス感染症に対する宿主因子依存性抗ウイルス薬の検索2017

    • Author(s)
      赤井佑三子、定成秀貴、茂木香保里、武本眞清、松原京子、大黒 徹、村山次哉
    • Organizer
      日本薬学会第137回年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 抗ヒトサイトメガロウイルス活性のあるtricinはcyclin-dependent kinase 9を阻害する2017

    • Author(s)
      定成秀貴、杉原雄斗、藤本和宏、武本眞清、大黒 徹、村山次哉
    • Organizer
      第26回抗ウイルス療法学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 超強力な抗ヒトサイトメガロウイルス活性を有する新規化合物2017

    • Author(s)
      根間大貴、藤本和宏、二ノ宮真之、纐纈 守、杉原雄斗、定成秀貴、武本眞清、大黒 徹、村山次哉
    • Organizer
      第26回抗ウイルス療法学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Novel compounds having potent anti-human cytomegalovirus activity2017

    • Author(s)
      Tsugiya Murayama, Daiki Nema, Kazuhiro Fujimoto, Mamoru Koketsu, Masayuki Ninomiya, Hidetaka Sadanari, Masaya Takemoto, Tohru Daikoku
    • Organizer
      第65回日本ウイルス学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Inhibition of phosphorylation of RNA polymerase II C-terminal domein by anti-human cytomegalovirus drug tricin2017

    • Author(s)
      Hidetaka Sadanari, Yuto Sugihara, Kazuhiro Fujimoto, Masaya Takemoto, Tohru Daikoku, Tsugiya Murayama
    • Organizer
      第65回日本ウイルス学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 日和見ウイルス感染症に対する新規治療薬の開発―作用機序に関する分子基盤機構の解明―2017

    • Author(s)
      村山次哉
    • Organizer
      北陸大学特別助成成果発表会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Inhibitory effect of tricin on CCL2-CCR2 dependent human cytomegalovirus replication.2017

    • Author(s)
      Tsugiya Murayama, Hidetaka Sadanari, Masaya Takemoto, Keiko Matsubara, Tohru Daikoku
    • Organizer
      16th international congenital CMV conference and 16th international CMV/betaherpesvirus workshop
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CCL2/CCR2-dependent replication of human cytomegalovirus is inhibited by anti-inflammatory compound tricin2017

    • Author(s)
      Tsugiya Murayama, Daiki Nema, Hidetaka Sadanari, Masaya Takemoto, Tohru Daikoku, Naofumi Mukaida
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Sosiety
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] イネ科植物含有成分による宿主依存性抗ウイルス薬の検索2016

    • Author(s)
      村山次哉
    • Organizer
      日本薬学会北陸支部第128回例会
    • Place of Presentation
      北陸大学薬学部
    • Year and Date
      2016-11-27
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] イネ科植物含有成分によるヒトサイトメガロウイルスの増殖抑制効果2016

    • Author(s)
      赤井佑三子、定成秀貴、武本眞清、大黒 徹、村山次哉
    • Organizer
      第19回日本補完代替医療学会学術集会
    • Place of Presentation
      石川県文教会館
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 抗ヒトサイトメガロウイルス活性のあるtricinがインターフェロン誘導性遺伝子発現に影響を与える2016

    • Author(s)
      茂木香保里、定成秀貴、武本眞清、大黒 徹、村山次哉
    • Organizer
      第19回日本補完代替医療学会学術集会
    • Place of Presentation
      石川県文教会館
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 抗炎症薬によるヒトサイトメガロウイルス複製の抑制2016

    • Author(s)
      村山次哉、赤井佑三子、定成秀貴、山田理恵、武本眞清、大黒 徹
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
  • [Presentation] インターフェロン誘導性遺伝子発現に対する抗ヒトサイトメガロウイルス活性のあるtricinの影響について2016

    • Author(s)
      定成秀貴、茂木香保里、山田理恵、武本眞清、大黒 徹、村山次哉
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
  • [Presentation] 話題の感染症とバイオテロリズム2016

    • Author(s)
      村山次哉
    • Organizer
      平成28年度日本薬学図書館協議会研究集会
    • Place of Presentation
      北陸大学
    • Year and Date
      2016-08-25
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] CCL5依存性ヒトサイトメガロウイルス増殖のtricinによる抑制効果2016

    • Author(s)
      伊藤暁将、定成秀貴、山田理恵、松原京子、武本眞清、村山次哉
    • Organizer
      第26回抗ウイルス療法学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Presentation] 抗ヒトサイトメガロウイルス活性のあるtricinのインターフェロン誘導性遺伝子発現に対する影響について2016

    • Author(s)
      茂木香保里、定成秀貴、山田理恵、松原京子、武本眞清、村山次哉
    • Organizer
      第26回抗ウイルス療法学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Presentation] Inhibition of CCL2 dependent human cytomegalovirus replication by tricin.2016

    • Author(s)
      Tsugiya Murayama, Rie Yamada, Keiko Matsubara, Hidetaka Sadanari
    • Organizer
      17th International Congress on Infectious Diseases
    • Place of Presentation
      Hyderabad, India
    • Year and Date
      2016-03-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] CCL2-CCR2 に依存したヒトサイトメガロウイルスの複製2015

    • Author(s)
      村山次哉、三井田隆貴、山田理恵、定成秀貴、松原恵子
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡国際会議センター
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Presentation] STATのリン酸化に対する抗ヒトサイトメガロウイルス活性のあるtricinの影響について2015

    • Author(s)
      定成秀貴、武本眞清、山田理恵、村山次哉
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡国際会議センター
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Book] “化学療法の領域、特集・飛躍的に発展を見せる抗ウイルス薬”2017

    • Author(s)
      村山次哉
    • Publisher
      医薬ジャーナル社
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 化合物又はその塩、抗ウイルス剤、医薬組成物2017

    • Inventor(s)
      村山次哉、土田裕三、藤本和宏、定成秀貴 他
    • Industrial Property Rights Holder
      村山次哉、土田裕三、藤本和宏、定成秀貴 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 化合物又はその塩、抗ウイルス剤、医薬組成物2017

    • Inventor(s)
      村山次哉,土田裕三、二ノ宮真之、桜井大輔 他
    • Industrial Property Rights Holder
      村山次哉,土田裕三、二ノ宮真之、桜井大輔 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-04-21
    • Related Report
      2016 Research-status Report

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

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