Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides

Novel strategies in the design of HIV-1 fusion/entry inhibitors are based on the construction of dual-targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual-targeting peptides composed of peptide domains of E2 and E1 envelope proteins f...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2019-03, Vol.9 (1), p.3257-3257, Article 3257
Main Authors: Gomara, Maria J., Perez, Yolanda, Martinez, Javier P., Barnadas-Rodriguez, Ramon, Schultz, Anke, von Briesen, Hagen, Peralvarez-Marin, Alex, Meyerhans, Andreas, Haro, Isabel
Format: Article
Language:English
Subjects:
101/58
13
14/33
14/34
631/57/2270
631/92/611
Affinity
Antiviral activity
C-Terminus
E1 protein
Glycoprotein gp41
HIV
Human immunodeficiency virus
Humanities and Social Sciences
Membrane biophysics
Membrane fusion
Membranes
multidisciplinary
Peptides
Science
Science (multidisciplinary)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Novel strategies in the design of HIV-1 fusion/entry inhibitors are based on the construction of dual-targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual-targeting peptides composed of peptide domains of E2 and E1 envelope proteins from Human Pegivirus with the aim of targeting both the loop region and the fusion peptide domains of HIV-1 gp41. In a previous work, we described the inhibitory role of a highly conserved fragment of the E1 protein (domain 139–156) which interacts with the HIV-1 fusion peptide at the membrane level. Here, two different dual-targeting peptides, where this E1 peptide is located on the N- or the C-terminus respectively, have been chemically synthesized and their antiviral activities have been evaluated with HIV pseudotyped viruses from different clades. The study of the functional behaviour of peptides in a membranous environment attending to the peptide recognition of the target sites on gp41, the peptide conformation as well as the peptide affinity to the membrane, demonstrate that antiviral activity of the dual-targeting peptides is directly related to the peptide affinity and its subsequent assembly into the model membrane. The overall results point out to the necessity that fusion inhibitor peptides that specifically interfere with the N-terminal region of gp41 are embedded within the membrane in order to properly interact with their viral target.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-40125-4