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

Tahir Bashir,Selvaa Kumar C,Achhelal Pasi,Mandar Patgaonkar,Kudumula Venkata Rami Reddy,Eliseo A Eugenin

doi:10.1371/journal.pone.0124839

Abstract

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.

Highlights

AIDS (Acquired Immunodeficiency Syndrome), caused by Human Immunodeficiency Virus (HIV), is one of the leading causes of death worldwide [1]
No reported crystal structure of glycosylated gp120 of HIV-1 was available, we looked for glycosylated gp120 proteins of other retroviruses
CEM-GFP cells were simultaneously infected with HIV-1 and HIV-1 (VSV) (20ng/ml p24) for 1 hr and entry of these viruses into cells was measured in the presence and absence of HbAHP-25

Summary

Introduction

AIDS (Acquired Immunodeficiency Syndrome), caused by Human Immunodeficiency Virus (HIV), is one of the leading causes of death worldwide [1]. Several low-molecular-weight (LMW) compounds and antimicrobial peptides (AMPs), which interfere with the initial steps of virus entry either by targeting gp120, gp41 or CCR5/CXCR4 co-receptors, have been discovered [7,8,9,10,11,12,13,14]. Their efficacy in clinical settings remains to be established. Till date the anti-HIV potential of hemoglobin derived antimicrobial peptides has not been explored. To the best of our knowledge, this is the first report on an Hb-derived AMP with anti-HIV activity

Materials and Methods

Ethics Statement

Results

Discussion