Biophysical properties and antiviral activities of measles fusion protein derived peptide conjugated with 25-Hydroxycholesterol

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Measles virus (MV) infection is re-emerging, despite the availability of an effective vaccine. The mechanism of MV entry into a target cell relies on coordinated action between the MV hemagglutinin (H) receptor binding protein and the fusion envelope glycoprotein (F) which mediates fusion between the viral and cell membranes. Peptides derived from the C-terminal heptad repeat (HRC) of F can interfere with this process, blocking MV infection. As previously described, biophysical properties of HRC-derived peptides modulate their antiviral potency. In this work, we characterized a MV peptide fusion inhibitor conjugated to 25-hydroxycholesterol (25HC), a cholesterol derivative with intrinsic antiviral activity, and evaluated its interaction with membrane model systems and human blood cells. The peptide (MV–HC) has a 90% inhibitory concentration (IC90) several logs more advantageous than the equivalent peptide bearing a polyethylene glycol (PEG)-cholesterol moiety. In membrane interaction studies, MV–HC shows a preference for pure 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) monolayers and membranes rich in sphingomyelin, and interacts less with POPC:cholesterol membranes. MV–HC tends to self-aggregate in aqueous solution, in a concentration-dependent manner. Our results suggest that increased membrane interaction dynamicity results from 25HC conjugation, with a concomitant increase in peptide antiviral efficacy.This work was supported by Fundação para a Ciência e Tecnologia—Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) grant PTDC/BBB-BQB/3494/2014, and NIH AI119762, AI121349, and NS091263 to M.P. B.G. also acknowledges FCT-MCTES fellowship SPRH/BD/52431/2013.