期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1991
卷号：88
期号：19
页码：8495-8499
DOI：10.1073/pnas.88.19.8495
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Several 2',3'-dideoxy-3'-thiapyrimidine nucleosides were studied for their ability to inhibit hepatitis B virus (HBV) DNA replication in a HBV-transfected cell line (2.2.15). 2',3'-Dideoxy-3'-thiacytidine (SddC) and 5-fluoro-2',3'-dideoxy-3'-thiacytidine(5-FSddC) were found to be the most potent anti-HBV compounds of those examined. Both compounds resulted in nearly complete cessation of viral DNA replication at 0.5 microM, as monitored by the absence of both intracellular episomal and secreted viral DNAs. The HBV-specific RNAs were not reduced at concentrations that completely blocked HBV DNA replication, suggesting that the inhibitory target is HBV DNA synthesis. The antiviral action of SddC and 5-FSddC was reversible. The concentration of SddC and 5-FSddC required to inhibit 50% of 4-day cell growth in culture was 37 microM and more than 200 microM, respectively. Unlike 2',3'-dideoxycytidine, these two compounds do not affect mitochondrial DNA synthesis in cells at concentrations lower than that required to inhibit cell growth. In view of the potent and selective antiviral activity, both SddC and 5-FSddC should be further evaluated for the treatment of human HBV infection.
