Chemistry (Weinheim an der Bergstrasse, Germany) 2017 07 05() doi 10.1002/chem.201702531
Previous studies support the hypothesis that the envelope GB virus C E1 protein interferes HIV-1 entry and a peptide, derived from the region (139-156) of this protein, has defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the peptide structural features which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction of with the proposed viral target (the HIV-1 fusion peptide). We report the peptide structure determined by NMR spectroscopy in DPC micelles solved using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (peptide-peptide titration, diffusion NMR and addition of paramagnetic relaxation agents) allows the proposal of an inhibition mechanism. We conclude that an 18-mer peptide from non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure, inhibits HIV-1 by binding to the HIV-1 fusion peptide at membrane level interfering with those domains in HIV-1 that are critical for stabilizing the six-helix bundle formation in a membranous environment.