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.

Highlights

  • Human respiratory diseases caused by the Paramyxoviridae family of viruses are a serious worldwide concern that affect the human population in all of its strata

  • We recently showed that conjugation of cholesterol and PEG24 to a fusion inhibitory peptide derived from this HPIV3-HRC peptide resulted in broad-spectrum antiviral activity [21]

  • We showed that peptides derived from the HRC domain of paramyxovirus F proteins have broad-spectrum antiviral activity, inhibiting fusion and entry mediated by HPIV3 and Nipah virus (NiV) [21]

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Summary

Introduction

Human respiratory diseases caused by the Paramyxoviridae family of viruses are a serious worldwide concern that affect the human population in all of its strata. Human parainfluenza viruses (HPIVs), either respiroviruses (HPIV1 and HPIV3) or rubulaviruses (HPIV2 and HPIV4), are common causes of significant lower respiratory tract disease including pneumonia. Documented HPIV infection accounts for 30–40% of all acute respiratory tract infections in children [1]. The zoonotic paramyxovirus Nipah virus (NiV) emerged in the human population from its bat reservoir via pig intermediate hosts, but has been transmitted directly between humans and represents a global health risk [2]. Human infection results in a range of outcomes from asymptomatic infection to a severe acute respiratory disease and fatal encephalitis, Molecules 2017, 22, 1190; doi:10.3390/molecules22071190 www.mdpi.com/journal/molecules

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