INHIBITION OF THE REPLICATION OF HEPATITIS-B VIRUS INVITRO BY 2',3'-DIDEOXY-3'-THIACYTIDINE AND RELATED ANALOGS
INHIBITION OF THE REPLICATION OF HEPATITIS-B VIRUS INVITRO BY 2',3'-DIDEOXY-3'-THIACYTIDINE AND RELATED ANALOGS
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DOI：
10.1073/pnas.88.19.8495
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发表时间：
1991-10-01
影响因子：
11.1
通讯作者：
CHENG, YC
中科院分区：
文献类型：
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作者：
DOONG, SL;TSAI, CH;CHENG, YC
研究了几种 2',3'-双脱氧-3'-硫杂嘧啶核苷在 HBV 转染细胞系中抑制乙型肝炎病毒 (HBV) DNA 复制的能力 (2.2.15)。 2',3'-二脱氧-3'-硫胞苷 (SddC) 和 5-氟-2',3'-二脱氧-3'-硫胞苷 (5-FSddC) 被发现是这些检查中最有效的抗 HBV 化合物。 通过细胞内附加型和分泌型病毒 DNA 的缺失进行监测，两种化合物在 0.5-mu-M 浓度时几乎完全停止病毒 DNA 复制。 HBV 特异性 RNA 在完全阻断 HBV DNA 复制的浓度下并未减少，表明抑制目标是 HBV DNA 合成。 SddC 和 5-FSddC 的抗病毒作用是可逆的。 抑制培养物中 4 天细胞生长 50% 所需的 SddC 和 5-FSddC 浓度分别为 37-mu-M 和超过 200-mu-M。 与 2',3'-二脱氧胞苷不同，这两种化合物在浓度低于抑制细胞生长所需的浓度时不会影响细胞中线粒体 DNA 的合成。 鉴于 SddC 和 5-FSddC 具有强效和选择性的抗病毒活性，应进一步评估其对人类 HBV 感染的治疗作用。
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-mu-M, 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-mu-M and more than 200-mu-M, 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.