新規核酸アナログ4'-C-cyano-2-amino-2'-deoxyadenosine,4'-C-cyano-2'-deoxyguanosineは薬剤耐性B型肝炎ウイルス変異株に対して有効である  [in Japanese] Novel 4'-modified nucleoside analogs exert antiviral replication against hepatitis B virus with drug resistance mutations  [in Japanese]

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Author(s)

    • 林 佐奈衣 Hayashi Sanae
    • 名古屋市立大学大学院医学研究科病態医科学 Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
    • 向後 悟 Kohgo Satoru
    • 国立研究開発法人国立国際医療研究センター|崇城大学 National Center for Global Health and Medicine|Sojo University
    • 満屋 裕明 Mitsuya Hiroaki
    • Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States|国立研究開発法人国立国際医療研究センター|熊本大学医学部付属病院血液内科・感染免疫診療部 Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health|National Center for Global Health and Medicine|Departments of Hematology, Rheumatology, and Clinical Immunology & Infectious Disease, Kumamoto University Graduate School of Medical Sciences
    • 田中 靖人 Tanaka Yasuhito
    • 名古屋市立大学大学院医学研究科病態医科学 Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
    • 高松 悠樹 Takamatsu Yuki
    • Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health
    • 前田 賢次 Maeda Kenji
    • Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States|国立研究開発法人国立国際医療研究センター Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health|National Center for Global Health and Medicine
    • 村上 周子 Murakami Shuko
    • 名古屋市立大学大学院医学研究科病態医科学 Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
    • 尾曲 克己 Omagari Katsumi
    • 名古屋市立大学大学院医学研究科病態医科学 Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
    • 松居 剛志 Matsui Takeshi
    • 名古屋市立大学大学院医学研究科病態医科学|手稲渓仁会病院消化器病センター Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences|Center for Gastroenterology, Teine Keijinkai Hospital
    • 五十川 正記 Isogawa Masanori
    • 名古屋市立大学大学院医学研究科病態医科学 Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
    • 渡邊 綱正 Watanabe Tsunamasa
    • 名古屋市立大学大学院医学研究科病態医科学 Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences

Abstract

Novel nucleoside analogues (NAs), 4'-C-cyano-2-amino-2'-deoxyadenosine (CAdA) and 4'-C-cyano-2'-deoxyguanosine (CdG) in lesser concentration strongly suppressed HIV-1 as well as viral replication of HBV clones with Adefovir resistance mutation (rtA181T/N236T) (ADVr) or Entecavir resistance mutations (ETVr1: rtL180M/M204V/S202G, ETVr2: rtL180M/M204V/I163V/A186T) <i>in vitro</i>. Moreover, we inoculated HBV wild or mutant strain (ETVr1) to chimeric mice with human hepatocytes, and administered CAdA and CdG. The <i>in vivo</i> experiments showed that CAdA/CdG significantly had greater levels of HBV reduction during 3 and 14 days in the wild group, compared with ETV. CAdA/CdG also elicited significantly greater levels of HBV reduction by day 7 in ETVr1 group. In conclusion, CAdA and CdG exert potent anti-HBV activity against both ETVr and ADVr, indicating new therapeutic option.

Journal

  • Kanzo

    Kanzo 57(6), 299-301, 2016

    The Japan Society of Hepatology

Codes

  • NII Article ID (NAID)
    130005160949
  • NII NACSIS-CAT ID (NCID)
    AN00047770
  • Text Lang
    JPN
  • ISSN
    0451-4203
  • NDL Article ID
    027435656
  • NDL Call No.
    Z19-130
  • Data Source
    NDL  J-STAGE 
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