Inhibition of reverse transcriptase activity of hepatitis B virus polymerase by β-l-D4A-TP.
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.
Wang
X Y
XY
Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, PR China.
Gao
L L
LL
Hu
Z H
ZH
Wang
H L
HL
Deng
F
F
Jin
J S
JS
D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014764:Viral Proteins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins; D016048:Dideoxyadenosine; C075923:2'3'-didehydro-2'3'-dideoxyadenosine; D012194:RNA-Directed DNA Polymerase