期刊
MOLECULES
卷 22, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/molecules22111869
关键词
measles virus; fusion; peptide; 25-hydroxycholesterol
资金
- Fundacao para a Ciencia e Tecnologia-Ministerio da Ciencia, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) [PTDC/BBB-BQB/3494/2014]
- NIH [AI119762, AI121349, NS091263]
- FCT-MCTES [SPRH/BD/52431/2013]
- Fundação para a Ciência e a Tecnologia [PTDC/BBB-BQB/3494/2014] Funding Source: FCT
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.
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