Schröder I, Holmgren B, Oberg M, Löfgren B
Department of Medical Microbiology, University of Lund, Sweden.
Antiviral Res. 1998 Jan;37(1):57-66. doi: 10.1016/s0166-3542(97)00057-0.
The fluorinated guanosine analog 2',3'-dideoxy-3'-fluoroguanosine (FLG) has been shown to have an effect on duck hepatitis B virus (DHBV) in vivo and in vitro. In this study the inhibitory effect of FLG on DHBV and human hepatitis B virus (HBV) was evaluated in vitro. Cell lines transfected either with DHBV or HBV DNA and primary duck hepatocyte cell cultures were used. Virus production was analysed by PCR and a quantitative PCR was established for DHBV for determination of the inhibitory concentrations of the drug. 50% inhibition was achieved with an FLG concentration of 0.2 microg/ml (0.7 microM) and 90% inhibition was observed with an FLG concentration of 1.0 microg/ml (3.7 microM) using the DHBV transfected cell line. FLG showed an effect on DHBV production in primary duck hepatocyte cell cultures at concentrations down to 0.1 microg/ml (0.4 microM). However, the DHBV production returned to pre-treatment levels within a few days after cessation of treatment. HBV production in transfected cell lines was also inhibited by FLG. Both DHBV and HBV DNA-polymerases were inhibited by FLG triphosphate and 50% inhibition was observed at a concentration of 0.05 microg/ml (0.1 microM) for DHBV and 0.03 microg/ml (0.05 microM) for HBV. FLG is an efficient inhibitor of DHBV replication both in vivo and in vitro and of HBV in vitro which makes it a good candidate for treatment of HBV infections. However, it does not completely eliminate the virus since a relapse in virus production was observed when treatment was withdrawn. Therefore it would be interesting to evaluate FLG in combination with other types of anti-HBV drugs.
氟化鸟苷类似物2',3'-二脱氧-3'-氟鸟苷（FLG）已被证明在体内和体外对鸭乙型肝炎病毒（DHBV）均有作用。在本研究中，对FLG在体外对DHBV和人乙型肝炎病毒（HBV）的抑制作用进行了评估。使用了转染DHBV或HBV DNA的细胞系以及原代鸭肝细胞培养物。通过PCR分析病毒产生情况，并建立了用于DHBV的定量PCR以测定药物的抑制浓度。使用转染DHBV的细胞系时，FLG浓度为0.2微克/毫升（0.7微摩尔）时实现了50%的抑制，FLG浓度为1.0微克/毫升（3.7微摩尔）时观察到90%的抑制。在原代鸭肝细胞培养物中，FLG浓度低至0.1微克/毫升（0.4微摩尔）时就对DHBV产生有影响。然而，停药后几天内DHBV产生又恢复到治疗前水平。转染细胞系中的HBV产生也受到FLG的抑制。DHBV和HBV DNA聚合酶均被三磷酸FLG抑制，DHBV在浓度为0.05微克/毫升（0.1微摩尔）时观察到50%的抑制，HBV在浓度为0.03微克/毫升（0.05微摩尔）时观察到50%的抑制。FLG在体内和体外都是DHBV复制的有效抑制剂，在体外也是HBV的有效抑制剂，这使其成为治疗HBV感染的良好候选药物。然而，它并不能完全清除病毒，因为停药后观察到病毒产生出现复发。因此，评估FLG与其他类型抗HBV药物联合使用将是很有意义的。
