[Effect and mechanism of beta-L-D4A (a novel nucleoside analog) against hepatitis B virus].
OBJECTIVE
To explore the effect and the molecular targets of anti-hepatitis B virus (HBV) by beta-L-D4A in vitro.


METHODS
2.2.15 cells were cultured and treated with various concentrations of beta-L-D4A for 6 hours, then the effect of anti-HBV was examined by Southern blot and the replicating core particles from the cells were isolated. The endogenous polymerase reaction and activity gel experiment were performed to monitor the activities of the DNA polymerase and reverse transcriptase.


RESULTS
The replication of HBV DNA was inhibited in a dose-dependent manner. The endogenous polymerase reaction showed both the two enzymatic activities were irreversibly inactivated in a concentration -dependent manner, with IC50 at 0.51 micromol/L and 0.55 micromol/L, respectively. But the activities of DNA polymerase and reverse transcriptase were found to remain active by activity gel with exogenous templates.


CONCLUSIONS
The mechanism of inhibiting HBV replication by beta-L-D4A may be in that either the DNA replication priming is blocked or the elongation of DNA chain is terminated irreversibly.
Wu
Jin-ming
JM
nstitute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, China.
Lin
Ju-sheng
JS
Xie
Na
N
Jiang
Feng-chao
FC
Liang
Kuo-huan
KH
D000998:Antiviral Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000096:biosynthesis; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D019384:Nucleic Acid Synthesis Inhibitors; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D019384:Nucleic Acid Synthesis Inhibitors; D016048:Dideoxyadenosine; C075923:2'3'-didehydro-2'3'-dideoxyadenosine