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Development of antiviral agents targeting ATP-mediated excision

Research Project

Project/Area Number 25670255
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionTohoku University

Principal Investigator

Kodama Eiichi  東北大学, 医学(系)研究科(研究院), 講師 (50271151)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsHIV / 薬物相互作用 / 耐性 / 核酸誘導体 / HIV
Outline of Final Research Achievements

In this study, we tried to expand our findings of ATP-medicated nucleotide excision inhibition, to biochemical, pharmacological, and structural aspects of DNA polymerases, via HIV reverse transcriptase as a model enzyme. We have established a novel assay system and screened over 5000 chemical compounds developed in the Tohoku University. Employing the identified several hits, structure-activity relation analysis is now in progress. In addition, we demonstrated that inhibitors for HIV reverse transcriptase appear to be experimentally suitable candidate to control differention process of mouse oocyte. Here we demonstrate that antiviral agents are useful for wide-range chemical biology tools as well as medical purpose.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 2013

All Journal Article (13 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (1 results)

  • [Journal Article] Use of a Biosynthetic Intermediate to Explore the Chemical Diversity of Pseudo-natural Fungal Polyketides2015

    • Author(s)
      T. Asai*, K. Tsukada, S. Ise, N. Shirata, M. Hashimoto, I. Fujii, K. Gomi, K. Nakagawara, E. N. Kodama, Y, Oshima
    • Journal Title

      Nature Chem.

      Volume: 7 Issue: 9 Pages: 737-743

    • DOI

      10.1038/nchem.2308

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of the DNA polymerase and RNase H activities of HIV-1 reverse transcriptase and HIV-1 replication by Brasenia schreberi (Junsai) and Petasites japonicus (Fuki) components2015

    • Author(s)
      Tetsuro Hisayoshi, Mayu Shinomura, Kanta Yokokawa, Ikumi Kuze, Atsushi Konishi, Kumi Kawaji, Eiichi N. Kodama, Keishi Hata, Saori Takahashi, Satoru Nirasawa, Kiyoshi Yasukawa.
    • Journal Title

      Journal of Natural Medicines

      Volume: 69 Issue: 3 Pages: 432

    • DOI

      10.1007/s11418-015-0885-9

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of Vpr-binding derivative for use as a novel HIV-1 inhibitor.2015

    • Author(s)
      Hagiwara K, Ishii H, Murakami T, Takeshima SN, Chutiwitoonchai N, Kodama EN, Kawaji K, Kondoh Y, Honda K, Osada H, Tsunetsugu-Yokota Y, Suzuki M, Aida Y
    • Journal Title

      PLoS One

      Volume: 10 Issue: 12 Pages: e0145573-e0145573

    • DOI

      10.1371/journal.pone.0145573

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histone chaperone CAF-1 mediates repressive histone modifications to protect preimplantation mouse embryos from endogenous retrotransposon.2015

    • Author(s)
      Hatanaka Y, Inoue K, Oikawa M, Kamimura S, Ogonuki N, Kodam E, Ohkawa Y, Tsukada Y, Ogura A.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 112 Issue: 47 Pages: 14641-14646

    • DOI

      10.1073/pnas.1512775112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-HIV-1 activitydetermined byb-galactosidase activityin the multinuclear activation ofan indicator assay is comparable with that by a conventional focus counting method.2015

    • Author(s)
      Fusako Miyamoto, Kumi Kawaji, Shinya Oishi, Nobutaka Fujii, Mitsuo Kaku, and Eiichi N.Kodama.
    • Journal Title

      Antiviral Chemistry and Chemotherapy

      Volume: 24(2) Issue: 2 Pages: 77-82

    • DOI

      10.1177/2040206615614164

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 4’-Ethynyl-2-fluoro-2’-deoxyadenosine (EFdA) inhibits HIV-1 reverse transcriptase with multiple mechanisms.2014

    • Author(s)
      Eleftherios Michailidis, Andrew D. Huber, Emily M. Ryan, Yee T. Ong, Maxwell D. Leslie, Kayla B. Matzek, Kamalendra Singh, Bruno Marchand, Ariel N. Hagedorn, Karen A. Kirby, Lisa C. Rohan, Eiichi N. Kodama, Hiroaki Mitsuya, Michael A. Parniak, and Stefan G. Sarafianos.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 289 Issue: 35 Pages: 24533-24548

    • DOI

      10.1074/jbc.m114.562694

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Current studies on chronic active Epstein-Barr virus infection in Japan.2014

    • Author(s)
      Fujiwara S, Kimura H, Imadome K, Arai A, Kodama, E, Morio T, Shimizu N, and Wakiguchi H.
    • Journal Title

      Pediatr Int.

      Volume: 56 Issue: 2 Pages: 159-166

    • DOI

      10.1111/ped.12314

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Delayed emergence of HIV-1 variants resistant to 4’-ethynyl-2-fluoro-2’-deoxyadenosine: comparative sequential passage study with lamivudine, tenofovir, emtricitabine and BMS-9860012013

    • Author(s)
      Kenji Maeda, Darshan V Desai, Manabu Aoki, Hirotomo Nakata, Eiichi N Kodama, Hiroaki Mitsuya
    • Journal Title

      Antiviral Therapy

      Volume: 19 Issue: 2 Pages: 179-189

    • DOI

      10.3851/imp2697

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanism of Resistance to S138A Substituted Enfuvirtide and its Application to Peptide Design2013

    • Author(s)
      Kazuki Izumi, Kumi Kawaji, Fusasko Miyamoto, Kazuki Shimane, Kazuya Shimura, Yasuko Sakagami, Toshio Hattori, Kentaro Watanabe, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka, Mitsuo Kaku, Stefan G. Sarafianos, and Eiichi N. Kodama
    • Journal Title

      International Journal of Biochemistry and Cell Biology

      Volume: 45 Pages: 908-915

    • Related Report
      2013 Research-status Report
  • [Journal Article] HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains2013

    • Author(s)
      Kazuki Shimane, KumiKawaji, Fusako Miyamoto, Shinya Oishi, Kentaro Watanabe, YasukoSakagami, Nobutaka Fujii, Kazuya Shimura, Masao Matsuoka, Mitsuo Kaku, Stefan Sarafianos, and Eiichi Kodama
    • Journal Title

      Antimicrobal Agents and Chemotherapy

      Volume: 57 Pages: 4035-4038

    • Related Report
      2013 Research-status Report
  • [Journal Article] Hypersusceptibility Mechanism of Tenofovir-Resistant HIV to EFdA2013

    • Author(s)
      Eleftherios Michailidis, Emily M Ryan, Atsuko Hachiya, Karen A Kirby, Bruno Marchand, Maxwell D Leslie, Andrew D Huber, Yee T Ong, Jacob C Jackson, Kamalendra Singh, Eiichi N Kodama, Hiroaki Mitsuya, Michael A Parniak and Stefan G Sarafianos
    • Journal Title

      Retrovirology

      Volume: 10 Issue: 1 Pages: 65-65

    • DOI

      10.1186/1742-4690-10-65

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of combinations of 4'-ethynyl-2-fluoro-2'-deoxyadenosine with clinically used antiretroviral drugs2013

    • Author(s)
      Atsuko Hachiya, Aaron Reeve, Bruno Marchand, Eleftherios Michailidis, Yee Ong, Karen Kirby, Maxwell Leslie, Shinichi Oka, Eiichi Kodama, Lisa Rohan, Hiroaki Mitsuya, Michael Parniak, and Stefan Sarafianos
    • Journal Title

      Antimicrobal Agents and Chemotherapy

      Volume: 57 Pages: 4554-4558

    • Related Report
      2013 Research-status Report
  • [Journal Article] Sarafianos SG.Effects of substitutions at the 4' and 2 positions on the bioactivity of 4'-ethynyl-2-fluoro-2'-deoxyadenosine2013

    • Author(s)
      Kirby KA, Michailidis E, Fetterly TL, Steinbach MA, Singh K, Marchand B, Leslie MD, Hagedorn AN, Kodama EN, Marquez VE, Hughes SH, Mitsuya H, Parniak MA
    • Journal Title

      Antimicrobal Agents and Chemotherapy

      Volume: 57 Pages: 6254-6264

    • Related Report
      2013 Research-status Report
  • [Presentation] Structural Basis of Inhibition and Resistance Mechanism to EFdA, a Highly Potent NRTI.2015

    • Author(s)
      Zhe Li, Karen Kirby, Bruno Marchand, Michailidis Eleftherios, Eiichi Kodama, Hiroaki Mitsuya, Michael Parniak, Stefan Sarafianos.
    • Organizer
      The annual Conference on Retroviruses and Opportunistic Infections
    • Place of Presentation
      シアトル・アメリカ
    • Year and Date
      2015-02-23 – 2015-02-26
    • Related Report
      2014 Research-status Report

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

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