HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor

PLoS One. 2015 Apr 27;10(4):e0124839. doi: 10.1371/journal.pone.0124839. eCollection 2015.


Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • CD4 Antigens / metabolism*
  • Cell Line
  • Cell Survival / drug effects
  • Epitopes / immunology
  • Female
  • HIV Antibodies / immunology
  • HIV Core Protein p24 / metabolism
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Fusion Inhibitors / chemistry
  • HIV Fusion Inhibitors / pharmacology*
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / physiology*
  • Hemoglobins / chemistry
  • Hemoglobins / pharmacology*
  • Humans
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Rats
  • Virus Internalization / drug effects*
  • Young Adult


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Epitopes
  • HIV Antibodies
  • HIV Core Protein p24
  • HIV Envelope Protein gp120
  • HIV Fusion Inhibitors
  • HbAHP-25
  • Hemoglobins
  • Peptide Fragments
  • Peptides
  • alpha(A) globin

Grants and funding

The authors have no support or funding to report.