Novel 4'-modified nucleoside analogs exert antiviral replication against hepatitis B virus with drug resistance mutations

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  • Hayashi Sanae
    Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
  • Takamatsu Yuki
    Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health
  • Maeda Kenji
    Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health National Center for Global Health and Medicine
  • Murakami Shuko
    Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
  • Omagari Katsumi
    Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
  • Matsui Takeshi
    Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences Center for Gastroenterology, Teine Keijinkai Hospital
  • Isogawa Masanori
    Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
  • Watanabe Tsunamasa
    Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences
  • Karino Yoshiyasu
    Department of Gastroenterology, Sapporo Kosei General Hospital
  • Kohgo Satoru
    National Center for Global Health and Medicine Sojo University
  • Mitsuya Hiroaki
    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
  • Tanaka Yasuhito
    Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences

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Other Title
  • 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
  • シンキ カクサン アナログ 4'-C-cyano-2-amino-2'-deoxyadenosine,4'-C-cyano-2'-deoxyguanosine ワ ヤクザイ タイセイ Bガタ カンエンウイルス ヘンイカブ ニ タイシテ ユウコウ デ アル

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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) in vitro. Moreover, we inoculated HBV wild or mutant strain (ETVr1) to chimeric mice with human hepatocytes, and administered CAdA and CdG. The in vivo 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

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