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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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.
Kanzo 57(6), 299-301, 2016
The Japan Society of Hepatology