Trimeric heptad repeat synthetic peptides HR1 and HR2 efficiently inhibit HIV-1 entry

Biosci Rep. 2019 Sep 24;39(9):BSR20192196. doi: 10.1042/BSR20192196. Print 2019 Sep 30.


The trimeric heptad repeat domains HR1 and HR2 of the human immunodeficiency virus 1 (HIV-1) gp41 play a key role in HIV-1-entry by membrane fusion. To develop efficient inhibitors against this step, the corresponding trimeric-N36 and C34 peptides were designed and synthesized. Analysis by circular dichroism of monomeric and trimeric N36 and C34 peptides showed their capacities to adopt α-helical structures and to establish physical interactions. At the virological level, while trimeric-C34 conserves the same high anti-fusion activity as monomeric-C34, trimerization of N36-peptide induced a significant increase, reaching 500-times higher in anti-fusion activity, against R5-tropic virus-mediated fusion. This result was associated with increased stability of the N36 trimer peptide with respect to the monomeric form, as demonstrated by the comparative kinetics of their antiviral activities during 6-day incubation in a physiological medium. Collectively, our findings demonstrate that while the trimerization of C34 peptide had no beneficial effect on its stability and antiviral activity, the trimerization of N36 peptide strengthened both stability and antiviral activity. This approach, promotes trimers as new promising HIV-1 inhibitors and point to future development aimed toward innovative peptide fusion inhibitors, microbicides or as immunogens.

Keywords: AIDS; C34; HIV-1; N36; inhibitors; trimers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Circular Dichroism
  • Drug Design
  • HIV Envelope Protein gp41 / chemical synthesis
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / pharmacology
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / pathogenicity
  • Humans
  • Membrane Fusion / drug effects
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry*
  • Peptide Fragments / pharmacology
  • Protein Conformation, alpha-Helical


  • HIV Envelope Protein gp41
  • Peptide Fragments
  • peptide C34
  • peptide N36