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Updated: Aug 15, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance
Karine Alvarez1, Jérôme Deval, Boulbaba Selmi
1CNRS, UMR 6098, Architecture et Fonction des Macromolecules Biologiques, Marseille Cedex 9, France.
Abstract:
Alpha-boranophosphates suppress RT-mediated resistance when the catalytic rate of incorporation (kpol) of the analogue 5'-triphosphate is responsable for drug resistance, such as in the case of K65R mutant and ddNTPs, and Q151M toward AZTTP and ddNTPs. This suppression is also observed with BH3-d4T and BH3-3TC toward their clinically relevant mutants Q151M and M184V. Moreover, the presence of the borano (BH3-) group renders the incorporation of the analogue independent from amino-acid substitutions in RT. To our knowledge, this is the first example of rescue of polymerase activity by means of a nucleotide analogue.
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