Measles Virus Fusion Protein: Structure, Function and Inhibition

• Published in: Viruses Vol. 8; no. 4; p. 112
• Main Authors: Plattet, Philippe, Alves, Lisa, Herren, Michael, Aguilar, Hector C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 21.04.2016; MDPI AG
• Subjects: Antiviral Agents - pharmacology; Binding Sites; cell entry; Drug Discovery; fusion protein; Host-Pathogen Interactions; Humans; inhibitors and mechanisms of adaptation; Measles - drug therapy; Measles - virology; measles virus; Measles virus - drug effects; Measles virus - physiology; membrane fusion; Models, Molecular; neuroinvasion; Protein Binding; Protein Conformation; Protein Folding; Protein Interaction Domains and Motifs; Protein Multimerization; Receptors, Virus - chemistry; Receptors, Virus - metabolism; Review; structural changes; Structure-Activity Relationship; Viral Fusion Protein Inhibitors - pharmacology; Viral Fusion Proteins - antagonists & inhibitors; Viral Fusion Proteins - chemistry; Viral Fusion Proteins - metabolism; Virus Internalization; cell entry; fusion protein; neuroinvasion; inhibitors and mechanisms of adaptation; structural changes; measles virus; membrane fusion
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v8040112

Measles virus (MeV), a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV)-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options.