title: Antiviral activity of FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, against human and duck HBV replication.
abstract: BACKGROUND
  New drugs are needed to combat HBV infection. We investigated the anti-HBV activity of the deoxycytidine analogue FNC, which has anticancer activity and has been found to inhibit HCV replication.
  
  
  METHODS
  In this study, a human hepatoma HepG2.2.15 cell culture system and duck HBV (DHBV) infection model were used as the in vitro and in vivo models to evaluate the anti-HBV activity of FNC.
  
  
  RESULTS
  In the cell model, FNC effectively suppressed the secretion of the HBV antigens in a dose-dependent manner, with 50% effective concentration values of 0.037 μM for hepatitis B surface antigen and 0.044 μM for hepatitis B e antigen on day 9. Consistent with the HBV antigen reduction, FNC also reduced the HBV DNA level by 92.31% and 93.90% intracellularly and extracellularly, respectively. DHBV DNA levels were markedly reduced after treatment with the FNC at 0.5, 1.0 and 2.0 mg/kg•day dosages. The inhibition rate of FNC at the dose of 2.0 mg/kg•day reached 91.68% and 81.96%, in duck serum and liver, respectively, on day 10. Furthermore, significant liver histology restoration after FNC treatment was observed, as evaluated by the histopathological analysis.
  
  
  CONCLUSIONS
  FNC can evidently inhibit the replication of HBV in the HepG2.2.15 cell line in vitro and inhibits DHBV replication in ducks in vivo. It could be potentially developed into a new anti-HBV drug.
authors.affiliation: Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Zheng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Guo
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Le
authors.initials: L
authors.lastname: Tao
authors.forename: Lihong
authors.initials: L
authors.lastname: Dong
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Li
authors.forename: Haoyun
authors.initials: H
authors.lastname: An
authors.forename: Xuejun
authors.initials: X
authors.lastname: Yu
authors.forename: Qingduan
authors.initials: Q
authors.lastname: Wang
authors.forename: Junbiao
authors.initials: J
authors.lastname: Chang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004372:Ducks; D006509:Hepatitis B / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000145:classification* / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001386:Azides; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D003841:Deoxycytidine; D019259:Lamivudine; C540945:azvudine