In search of new inhibitors of HIV-1 replication: synthesis and study of 1-(2'-Deoxy-beta-D-Ribofuranosyl)-1,2,4-triazole-3-carboxamide as a selective viral mutagenic agent.
With the emergence of HIV strains resistant or cross-resistant to nearly all antiretroviral regimen, novel therapy approaches have to be considered. As a part of our current work on viral mutagenic compounds, we prepared 1-(2' -deoxy-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (2' -deoxy-ribavirin) and its 5' -triphosphate derivative. The nucleoside mutagenic activity was evaluated on HIV-1 NL4-3 in CEMx174 cell culture. After 2.5 months, no reduction on HIV-1 viability was observed. On the other hand, in vitro experiments with purified HIV-1 RT demonstrated that the triphosphate analog can be incorporated opposite to several natural nucleosides.
Vivet-Boudou
V
V
Architecture et Réactivité de l'ARN, Université Louis Pasteur, Strasbourg, France. v.vivet@bmc.u-strasbg.fr
Paillart
J-C
JC
Burger
A
A
Marquet
R
R
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016296:Mutagenesis / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D007093:Imidazoles