Efficacies of beta-L-D4A against Hepatitis B virus in 2.2.15 cells

World J Gastroenterol. 2008 Feb 28;14(8):1263-7. doi: 10.3748/wjg.14.1263.

Abstract

Aim: To investigate the antiviral effect of beta-L-enantiomer of 2',3'-didehydro-2',3'-dideoxyadenosine (beta-L-D4A) on 2.2.15 cells transfected with the hepatitis B virus (HBV) genome.

Methods: Lamivudine (3TC) as a positive control. Then, HBV DNA in treated 2.2.15 cells and the Hepatitis B surface antigen (HBsAg) in the culture supernatants were detected to determine the inhibitory effect of beta-L-D4A. At the same time, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to detect the survival ratio of 2.2.15 cells.

Results: beta-L-D4A has a dose-dependent inhibitory effect on HBV DNA replication; this effect was apparent when the concentration was above 1 mol/L. When beta-L-D4A was at the highest concentration, 100 mol/L, the HBsAg inhibition ratio was above 50%. The Therapeutic index (TI) of beta-L-D4A was above 2.1.

Conclusion: beta-L-D4A has a dose-dependent inhibitory effect on the replication of HBV DNA and the secretion of HBsAg at low toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cell Line
  • DNA Replication / drug effects
  • DNA, Viral / chemistry
  • Dideoxyadenosine / analogs & derivatives*
  • Dideoxyadenosine / pharmacology
  • Dose-Response Relationship, Drug
  • Hepatitis B / drug therapy*
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B virus / metabolism*
  • Humans
  • Lamivudine / pharmacology
  • Models, Chemical
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Tetrazolium Salts
  • Thiazoles
  • Lamivudine
  • Dideoxyadenosine
  • 2'3'-didehydro-2'3'-dideoxyadenosine
  • thiazolyl blue