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

摘要

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.