Synthesis and Primary Evaluation of Novel HIV-1 Inhibitors

Abstract

The overcoming of antiviral drug resistance is an important challenge in the treatment of HIV-1 infection.

According to the theory of viral error catastrophe, slightly increasing the mutation rate could exceed the error threshold for viability of a viral population and kill it. Investigation of this mechanism could lead to the discovery of new antiviral agents capable of bypassing viral resistance.

To this aim, we designed several modified nucleosides. We describe here the synthesis and partial evaluation of 8-amido-2′-deoxyadenosine. The supplementary amide group on the base should allow base-pairing with several natural nucleosides, thus creating supplementary mutations that would kill the virus.

Keywords:

• HIV-1
• antiviral drug resistance
• viral error catastrophe

Acknowledgments

We would like to Thank Philippe Wolff for his help in preparing and purifying oligonucleotides. This work is supported by the ANRS (Agence Nationale de Recherches sur le Sida), France.