Differential inhibition of HIV-1 and SIV envelope-mediated cell fusion by C34 peptides derived from the C-terminal heptad repeat of gp41 from diverse strains of HIV-1, HIV-2, and SIV

J Med Chem. 2005 Apr 21;48(8):3036-44. doi: 10.1021/jm049026h.


The spectrum of inhibition of human (HIV) and simian (SIV) immunodeficiency virus envelope (Env)-mediated cell fusion by C34, a 34 residue peptide corresponding to the C-heptad repeat of gp41 (residues 628-661 of HIV-1 Env), has been examined using a panel of five envelope glycoproteins, three from HIV-1 (LAV, SF162 and 89.6) and two from SIV (mac239 and mac316), and six C34 peptides derived from three strains of HIV-1 (LAV, N CM, and O CM), two strains of HIV-2 (EHO and ALI), and one strain of SIV (African Green Monkey, AGM). A quantitative vaccinia-based reporter gene cell fusion assay was employed. The inhibition data from the panel of 30 C34/envelope glycoprotein combinations, which can be fit to a simple activity relationship with IC(50) values spanning a range of over 4 orders of magnitude from 4 nM to 70 microM, permits one to rationalize both the potency and broadness of the inhibitory properties of the C34 peptides in terms of computed interaction free energies between the C34 peptides and the N-helical trimeric coiled-coil of gp41 and the helical propensities of the free C34 peptides. Of particular interest is the finding that the C34 peptide derived from the EHO strain of HIV-2 is a broad spectrum, highly potent inhibitor of Env-mediated cell fusion with IC(50) values spanning a very narrow range from only 4 to 25 nM over the entire panel of HIV-1 and SIV envelope glycoproteins tested. This result suggests that C34 from HIV-2 EHO may present a potentially useful therapeutic agent against diverse and/or resistant strains of HIV-1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Fusion
  • Cell Line
  • Chlorocebus aethiops
  • Circular Dichroism
  • Computer Simulation
  • Genes, Reporter
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / pharmacology*
  • HIV-1 / chemistry*
  • HIV-2 / chemistry*
  • Membrane Glycoproteins / chemistry*
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Protein Structure, Secondary
  • Retroviridae Proteins / chemistry*
  • Simian Immunodeficiency Virus / chemistry*
  • Thermodynamics
  • Vaccinia virus / genetics
  • Viral Envelope Proteins / physiology*


  • Anti-HIV Agents
  • HIV Envelope Protein gp41
  • Membrane Glycoproteins
  • Peptide Fragments
  • Retroviridae Proteins
  • SIV envelope protein gp41
  • Viral Envelope Proteins
  • peptide C34