HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor.
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.
Division of Molecular Immunology and Microbiology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Mumbai, India.
Tahir
T
Bashir
Department of Biological Sciences, Tata Institute for Fundamental Research, Mumbai, India.
Mandar
M
Patgaonkar
Department of Bioinformatics, School of Biotechnology and Bioinformatics, D.Y. Patil University, Navi Mumbai, India.
Selvaa C
SC
Kumar
Division of Molecular Immunology and Microbiology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Mumbai, India.
Achhelal
A
Pasi
Division of Molecular Immunology and Microbiology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Mumbai, India.
Kudumula Venkata Rami
KV
Reddy
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D016655:HIV Core Protein p24 / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D051381:Rats; D053586:Virus Internalization / Q000187:drug effects*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; C000604627:HbAHP-25; D006454:Hemoglobins; D010446:Peptide Fragments; D010455:Peptides; C070077:alpha(A) globin