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Helical peptides with disordered regions for measles viruses provide new generalized insights into fusion inhibitors.
- Source :
-
IScience [iScience] 2024 Jan 17; Vol. 27 (2), pp. 108961. Date of Electronic Publication: 2024 Jan 17 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Despite effective vaccines, measles virus (MeV) outbreaks occur sporadically. Therefore, developing anti-MeV agents remains important for suppressing MeV infections. We previously designed peptide-based MeV fusion inhibitors, M1 and M2, that target MeV class I fusion protein (F protein). Here, we developed a novel fusion inhibitor, MEK35, that exerts potent activity against M1/M2-resistant MeV variants. Comparing MEK35 to M1 derivatives revealed that combining disordered and helical elements was essential for overcoming M1/M2 resistance. Moreover, we propose a three-step antiviral process for peptide-based fusion inhibitors: (i) disordered peptides interact with F protein; (ii) the peptides adopt a partial helical conformation and bind to F protein through hydrophobic interactions; and (iii) subsequent interactions involving the disordered region of the peptides afford a peptide-F protein with a high-affinity peptide-F protein interaction. An M1-resistant substitution blocks the second step. These results should aid the development of novel viral fusion inhibitors targeting class I F protein.<br />Competing Interests: The authors declare that they have no conflict of interest with the contents of this article.<br /> (© 2024 The Authors.)
Details
- Language :
- English
- ISSN :
- 2589-0042
- Volume :
- 27
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- IScience
- Publication Type :
- Academic Journal
- Accession number :
- 38333694
- Full Text :
- https://doi.org/10.1016/j.isci.2024.108961