Towards improved anti-HIV peptides that prevent viral escape

摘要

Peptides based on the second heptad repeat (HR2) of viral class I fusion proteins are effective inhibitors of virus entry. One such fusion inhibitor (T20, enfuvirtide) has been approved for treatment of HTV-1 infection. Resistance to T20 often maps to position 38 in the peptide binding site of the HR1 domain of the viral Envelope protein. To better understand fusion inhibitor potency and resistance, we combined virological, computational, and biophysical experiments with comprehensive mutational analyses and tested resistance to T20 and the second and third generation inhibitors (T1249 and T2635) developed by Trimeris-Roche.