Abstract
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.
Highlights
IntroductionMeasles virus (MV) is a human virus of the Paramyxoviridae family and Morbillivirus genus [1]
Measles virus (MV) is a human virus of the Paramyxoviridae family and Morbillivirus genus [1].Despite the availability of a vaccine since 1963 and safe and effective immunization since the early 1980s, with a global drop in prevalence [2], measles is currently re-emerging and several recent outbreaks have occurred in developed countries
The membrane in agreement with our previous findings that correlated peptide efficacy to membrane dynamic interaction property conferred by cholesterol conjugation and increases the dynamicity of the kinetics interactions of interaction[56]
Summary
Measles virus (MV) is a human virus of the Paramyxoviridae family and Morbillivirus genus [1]. Despite the availability of a vaccine since 1963 and safe and effective immunization since the early 1980s, with a global drop in prevalence [2], measles is currently re-emerging and several recent outbreaks have occurred in developed countries. Infections are mostly associated with vaccine refusal, and occur in vaccinated persons exposed to this highly transmissible virus, and in the growing population of immunocompromised individuals [5]. The immune response elicited by vaccination varies widely within the population, the recommended two doses of vaccine are not a guarantee of an adequate protection [6,7], and immunocompromised people cannot be vaccinated with this live virus vaccine
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