Broad spectrum antiretroviral activity of 2',3'-dideoxynucleosides.

Abstract

Certain dideoxynucleosides have been shown to markedly inhibit the infectivity of human T-lymphotropic virus type III/lymphadenopathy-associated virus, the causative agent of acquired immunodeficiency syndrome (AIDS). Our present studies demonstrate that these drugs are broad spectrum antiretroviral agents capable of inhibiting the infectivity of evolutionarily divergent mammalian type C and animal lentiviruses. Under some conditions, virus infectivity could be inhibited by more than six orders of magnitude. However, the potency of these agents was shown to be greatly influenced by cell-specified determinants. Drug exposure during the initial 24 hr was almost as effective as prolonged treatment on the inhibition of a single cycle of virus infection and expression. Moreover, virus infection was shown directly to be inhibited at the level of proviral DNA synthesis. Thus the time period during which reverse transcription and provirus integration occur is the critical period required for drug action. Our findings have implications concerning strategies to be considered in attempts to utilize 2',3'-dideoxynucleosides in control and treatment of retrovirus-induced diseases of animals and humans.

• Authors: J E Dahlberg, H Mitsuya, S B Blam, S Broder, S A Aaronson
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 84 Issue 8 Pg. 2469-73 (Apr 1987) ISSN: 0027-8424 [Print] United States
• PMID: 3470806 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Deoxyribonucleosides

Topics

• Animals
• Antiviral Agents
• Cell Line
• DNA Replication (drug effects)
• Deoxyribonucleosides (pharmacology)
• Drug Evaluation, Preclinical
• HIV (drug effects)
• Retroviridae (drug effects)
• Species Specificity
• Structure-Activity Relationship
• Virus Replication (drug effects)