Design and evaluation of antiretroviral peptides corresponding to the C-terminal heptad repeat region (C-HR) of human immunodeficiency virus type 1 envelope glycoprotein gp41

Virology. 2010 Sep 15;405(1):157-64. doi: 10.1016/j.virol.2010.06.012. Epub 2010 Jul 2.

Abstract

Two alpha-helical heptad repeats, N-HR and C-HR, located in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, play an important role in membrane fusion by forming a 6-helix bundle. C34, a peptide mimicking C-HR, inhibits the formation of the 6-helix bundle; thus, it has potential as a novel antiretroviral compound. In order to improve the inhibitory effect of C34 on HIV-1 replication, we designed new C34-derived peptides based on computational analysis of the stable conformation of the 6-helix bundle. Newly designed peptides showed a stronger inhibitory effect on the replication of recombinant viruses containing CRF01_AE, subtype B or subtype C Env than C34 or a fusion inhibitor, T-20. In addition, these peptides inhibited the replication of a T-20-resistant virus. We propose that these peptides could be applied to develop novel antiretroviral compounds to inhibit the replication of various subtypes of HIV-1 as well as of T-20-resistant variants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Retroviral Agents / pharmacology*
  • Drug Design
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / genetics
  • HIV Envelope Protein gp41 / metabolism*
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protein Conformation
  • Virus Replication / drug effects

Substances

  • Anti-Retroviral Agents
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Peptides
  • peptide C34