β-l-D4A-TP对乙型肝炎病毒聚合酶逆转录酶活性的抑制作用。

Inhibition of reverse transcriptase activity of hepatitis B virus polymerase by β-l-D4A-TP.

作者信息

Wang X Y, Gao L L, Hu Z H, Wang H L, Deng F, Jin J S

机构信息

Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, PR China.

出版信息

Acta Virol. 2008;52(1):47-52.

PMID:18459835

Abstract

β-L-enantiomer of 2',3'-didehydro-2',3'-dideoxyadenosine-5'-triphosphate (β-L-D4A-TP) has previously been proven to inhibit the replication of viral DNA in the Hep G2 2.2.15 cells and in transgenic mouse harboring 1.3-fold-overlength genome of Hepatitis B virus (HBV). To study the inhibition mechanism of the nucleoside analog β-L-D4A-TP, a polymerase reaction in vitro with the recombinant HBV nucleocapsids was conducted to determine the exact mode of inhibition of the HBV replication by β-L-D4A-TP. The HBV viral DNA and viral DNA-polymerase complex formed in the polymerase reaction were assayed. The results of this study showed that β-L-D4A-TP inhibited the replication of HBV DNA by inactivating the reverse transcriptase (RT) activity in a concentration-dependent manner. The kinetics of β-L-D4A-TP inhibition of the RT activity was the result of an apparent competitive inhibition with dATP.

摘要

2',3'-二脱氢-2',3'-二脱氧腺苷-5'-三磷酸（β-L-D4A-TP）的β-L-对映体先前已被证明可抑制乙型肝炎病毒（HBV）1.3倍超长基因组的Hep G2 2.2.15细胞和转基因小鼠中病毒DNA的复制。为了研究核苷类似物β-L-D4A-TP的抑制机制，进行了重组HBV核衣壳的体外聚合酶反应，以确定β-L-D4A-TP对HBV复制的确切抑制模式。对聚合酶反应中形成的HBV病毒DNA和病毒DNA-聚合酶复合物进行了分析。本研究结果表明，β-L-D4A-TP通过以浓度依赖性方式使逆转录酶（RT）失活来抑制HBV DNA的复制。β-L-D4A-TP对RT活性的抑制动力学是与dATP明显竞争性抑制的结果。