7-Deaza-7-fluoro modification confers on 4'-cyano-nucleosides potent activity against entecavir/adefovir-resistant HBV variants and favorable safety.

ABSTRACT: We designed, synthesized and identified a novel nucleoside derivative, 4'-C-cyano-7-deaza-7-fluoro-2'-deoxyadenosine (CdFA), which exerts potent anti-HBV activity (IC₅₀ ~26 nM) with favorable hepatocytotoxicity (CC₅₀ ~56 μM). Southern blot analysis using wild-type HBV (HBV_WT)-encoding-plasmid-transfected HepG2 cells revealed that CdFA efficiently suppresses the production of HBV_WT (IC₅₀ = 153.7 nM), entecavir (ETV)-resistant HBV carrying L180M/S202G/M204V substitutions (HBV_ETV^R; IC₅₀ = 373.2 nM), and adefovir dipivoxil (ADV)-resistant HBV carrying A181T/N236T substitutions (HBV_ADV^R; IC₅₀₌192.6 nM), whereas ETV and ADV were less potent against HBV_ETV^R

SUBMITTER: Hayashi S 

PROVIDER: S-EPMC7164687 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature