Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

摘要: Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold viability. Their existence as quasi-species has pioneered concept “lethal mutagenesis” that prompted us synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent an accumulation deleterious mutations HIV-1 genome. However, testing all potentially mutagenic compounds cell-based assays is tedious costly. Here, we describe two simple vitro biophysical/biochemical allow prediction potential deoxyribonucleoside analogues. The first assay compares thermal stabilities matched mismatched base pairs DNA duplexes containing or not follows. A promising candidate should display a small destabilization pair compared natural smallest gap possible between pairs. From this assay, predicted our compounds, 5-hydroxymethyl-2′-deoxyuridine 5-hydroxymethyl-2′-deoxycytidine, be mutagenic. second reverse transcription assesses synthesis opposite inserted into template strand subsequent extension newly synthesized Once again, only 5-hydroxymethyl-2′-deoxycytidine are efficient mutagens. predictive fast easy line screens was confirmed by detailed analysis spectrum induced because were found increase frequency 3.1- 3.4-fold, respectively.