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. 2017 Jul 15;22(7):1190.
doi: 10.3390/molecules22071190.

Antiviral Lipopeptide-Cell Membrane Interaction Is Influenced by PEG Linker Length

Marcelo T Augusto  1 , Axel Hollmann  2   3   4 , Matteo Porotto  5   6 , Anne Moscona  7   8   9   10 , Nuno C Santos  11
Affiliations

Antiviral Lipopeptide-Cell Membrane Interaction Is Influenced by PEG Linker Length

Marcelo T Augusto et al. Molecules. .

Abstract

A set of lipopeptides was recently reported for their broad-spectrum antiviral activity against viruses belonging to the Paramyxoviridae family, including human parainfluenza virus type 3 and Nipah virus. Among them, the peptide with a 24-unit PEG linker connecting it to a cholesterol moiety (VG-PEG24-Chol) was found to be the best membrane fusion inhibitory peptide. Here, we evaluated the interaction of the same set of peptides with biomembrane model systems and isolated human peripheral blood mononuclear cells (PBMC). VG-PEG24-Chol showed the highest insertion rate and it was among the peptides that induced a larger change on the surface pressure of cholesterol rich membranes. This peptide also displayed a high affinity towards PBMC membranes. These data provide new information about the dynamics of peptide-membrane interactions of a specific group of antiviral peptides, known for their potential as multipotent paramyxovirus antivirals.

Keywords: antiviral; cholesterol; membranes; paramyxoviruses; peptides.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Surface pressure perturbation of lipid monolayers. (A) Changes in the surface pressure as a function of concentration of VG peptides (or DMSO) added to POPC:Chol 2:1 monolayers. (B) Maximum surface pressure perturbation achieved at 0.63 µM of peptide (dashed line in A) or DMSO. (C) Variation of the surface pressure of POPC:Chol 2:1 monolayers as a function of time after injection of VG peptides at a final concentration of 0.2 µM. C1 is a section of the first 100 s of the kinetic assay showing the two-phase behavior of VG-PEG24-Chol, characterized by a fast membrane insertion during the first 20 s (a), followed by a slower interaction over time (b).
Figure 2
Figure 2
Fusion inhibitory peptides’ interaction with di-8-ANEPPS labeled liposomes and cells. Binding profiles of VG peptides to LUVs of POPC (A) or POPC:Chol 2:1 (B), and to human PBMC (C), obtained by plotting the di-8-ANEPPS excitation ratio R (I455/I525, normalized to the initial value), as a function of peptide concentration.
See this image and copyright information in PMC

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