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Establishment of virtual assay system by molecular dynamic simulation of HCV antiviral resistance

Research Project

Project/Area Number 26670375
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionHokkaido University

Principal Investigator

Sakamoto Naoya  北海道大学, 医学(系)研究科(研究院), 教授 (10334418)

Co-Investigator(Kenkyū-buntansha) ENDO TOSHINORI  北海道大学, 情報科学研究科, 教授 (00323692)
SUDA GOKI  北海道大学, 医学研究科, 特任助教 (20447460)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsウイルス学 / 肝炎ウイルス / 分子動力学シミュレーション / C型肝炎 / 抗ウイルス療法 / 薬剤耐性変異
Outline of Final Research Achievements

1. We conducted a molecular dynamic simulation of NS5A protein, its dimer and NS5A inhibitor (daclatasvir), and designated individual optimal 3D structures.
2. We conducted a molecular dynamic simulations of NS5A dimer and daclatasvir on the ER membrane.
3. We conducted an in-vitro assay by using HCV replicon system and confirmed expected effects of resistance-associated substitutions.

Report

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

    (14 results)

All 2016 2015 2014

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 9 results,  Acknowledgement Compliant: 5 results)

  • [Journal Article] Prevalence and characteristics of naturally occurring sofosbuvir resistance-associated variants in patients with hepatitis C virus genotype 1b infection2016

    • Author(s)
      Ito J, Suda G, Yamamoto Y, Nagasaka A, Furuya K, Kumagai K, Kikuchi H, Miyagishima T, Kobayashi T, Kimura M, Yamasaki K, Umemura M, Izumi T, Tsunematsu S, Sato F, Tsukuda Y, Terashita K, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto
    • Journal Title

      Hepatol Res

      Volume: in press Issue: 13 Pages: 1294-1303

    • DOI

      10.1111/hepr.12685

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Viral life cycle of hepatitis B virus : host factors and druggable targets.2016

    • Author(s)
      Morikawa K, Suda G, Sakamoto N
    • Journal Title

      Hepatol Res

      Volume: EPub Issue: 9 Pages: 871-877

    • DOI

      10.1111/hepr.12650

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Efficacy and safety of daclatasvir and asunaprevir combination therapy in chronic hemodialysis patients with chronic hepatitis C.2016

    • Author(s)
      Suda G, Kudo M, Nagasaka A, Furuya K, Yamamoto Y, Kobayashi T, Shinada K, Tateyama M, Konno J, Tsukuda Y, Yamasaki K, Kimura M, Umemura M, Izumi T, Tsunematsu S, Sato F, Terashita K, Nakai M, Horimoto H, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N
    • Journal Title

      J Gastroenterol Hepatol

      Volume: EPub Issue: 7 Pages: 733-740

    • DOI

      10.1007/s00535-016-1162-8

    • NAID

      120006313426

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma2016

    • Author(s)
      Terashita K, Chuma M, Hatanaka Y, Hatanaka K, Mitsuhashi T, Yokoo H, Ohmura T, Ishizu H, Muraoka S, Nagasaka A, Tsuji T, Yamamoto Y, Kurauchi N, Shimoyama N, Toyoda H, Kumada T, Kaneoka Y, Maeda A, Ogawa K, Natsuizaka M, Kamachi H, Kakisaka T, Kamiyama T, Taketomi A, Matsuno Y, Sakamoto N
    • Journal Title

      J Clin Pathol

      Volume: in press Issue: 7 Pages: 593-599

    • DOI

      10.1136/jclinpath-2015-203115

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals.2015

    • Author(s)
      N. Nishida, J. Ohashi, M. Sugiyama, T. Tsuchiura, K. Yamamoto, K. Hino, M. Honda, S. Kaneko, H. Yatsuhashi, K. Koike, O. Yokosuka, E. Tanaka, A. Taketomi, M. Kurosaki, N. Izumi, N. Sakamoto, Y. Eguchi, T. Sasazuki, K. Tokunaga, and M. Mizokami
    • Journal Title

      Tissue Antigens

      Volume: 5 Issue: 6 Pages: 406-412

    • DOI

      10.1111/tan.12684

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Amino acid polymorphisms in hepatitis C virus core affect infectious virus production and major histocompatibility complex class I molecule expression2015

    • Author(s)
      Tasaka-Fujita M, Sugiyama N, Kang W, Masaki T, Murayama A, Yamada N, Sugiyama R, Tsukuda S, Watashi K, Asahina Y, Sakamoto N, Wakita T, Shin EC, Kato T
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 13994-14002

    • DOI

      10.1038/srep13994

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions.2015

    • Author(s)
      Suda G, Yamamoto Y, Nagasaka A, Furuya K, Kudo M, Chuganji Y, Tsukuda Y, Tsunematsu S, Sato F, Terasita K, Nakai M, Horimoto H, Sho T, Natsuizaka M, Ogawa K, Ohnishi S, Chuma M, Fujita Y, Abe R, Taniguchi M, Nakagawa M, Asahina Y, Sakamoto N
    • Journal Title

      Hepatol Res

      Volume: 印刷中 Issue: 8 Pages: 837-45

    • DOI

      10.1111/hepr.12421

    • NAID

      120005820706

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions.2015

    • Author(s)
      Chuma M, Terashita K, Sakamoto N
    • Journal Title

      Hepatol Res

      Volume: 印刷中 Issue: 10

    • DOI

      10.1111/hepr.12459

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C.2015

    • Author(s)
      Iio E, Matsuura K, Nishida N, Maekawa S, Enomoto N, Nakagawa M, Sakamoto N, Yatsuhashi H et al.
    • Journal Title

      Hum Genet

      Volume: 134 Issue: 3 Pages: 279-289

    • DOI

      10.1007/s00439-014-1520-7

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired induction of IL28B and expression of IFNλ4 associated with non-response to interferon-based therapy in chronic hepatitis C.2015

    • Author(s)
      Murakawa M, Asahina Y, Nakagawa M, Sakamoto N, Nitta S, Kusano-Kitazume A, Watanabe T, Kawai-Kitahata F, Otani S, Taniguchi M, Goto F, Nishimura-Sakurai Y, Itsui Y, Azuma S, Kakinuma S, Watanabe M
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 印刷中 Issue: 6 Pages: 1075-84

    • DOI

      10.1111/jgh.12902

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial.2015

    • Author(s)
      Mizokami M, Yokosuka O, Takehara T, Sakamoto N, Korenaga M, Mochizuki H, Nakane K, Enomoto H, Ikeda F, Yanase M, Toyoda H, Genda T, Umemura T, Yatsuhashi H, Ide T et al.
    • Journal Title

      Lancet Infect Dis

      Volume: 印刷中 Issue: 6 Pages: 645-653

    • DOI

      10.1016/s1473-3099(15)70099-x

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type.2014

    • Author(s)
      Matsuura K, Tanaka Y, Watanabe T, Fujiwara K, Orito E, Kurosaki M, Izumi N, Sakamoto N, Enomoto N, Yatsuhashi H, Kusakabe A, Shinkai N, Nojiri S, Joh T, Mizokami M.
    • Journal Title

      J Viral Hepat.

      Volume: 21 Issue: 7 Pages: 466-474

    • DOI

      10.1111/jvh.12171

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] The J6JFH1 Strain of Hepatitis C Virus Infects Human B-Cells with Low Replication Efficacy.2014

    • Author(s)
      Nakai M, Seya T, Matsumoto M, Shimotohno K, Sakamoto N, Aly HH.
    • Journal Title

      Viral Immunol.

      Volume: 27 Issue: 6 Pages: 285-294

    • DOI

      10.1089/vim.2013.0140

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial.2014

    • Author(s)
      Omata M, Nishiguchi S, Ueno Y, Mochizuki H, Izumi N, Ikeda F, Toyoda H, Yokosuka O, Nirei K, Genda T, Umemura T, Takehara T, Sakamoto N, Nishigaki Y, Nakane K, Toda N, Ide T, Yanase M, Hino K et al.
    • Journal Title

      J Viral Hepat

      Volume: 21 Issue: 11 Pages: 762-768

    • DOI

      10.1111/jvh.12312

    • Related Report
      2014 Research-status Report
    • Peer Reviewed

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Published: 2014-04-04   Modified: 2017-05-10  

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