The pH-sensitive action of cholesterol-conjugated peptide inhibitors of influenza virus.
Cell Membrane
/ chemistry
Cholesterol
/ chemistry
Endocytosis
/ drug effects
Hemagglutinin Glycoproteins, Influenza Virus
/ chemistry
Humans
Hydrogen-Ion Concentration
Influenza, Human
/ genetics
Lipopeptides
/ chemistry
Orthomyxoviridae
/ genetics
Protein Binding
/ drug effects
Virus Internalization
/ drug effects
Cholesterol-tagging
Influenza virus
Lipopeptides
Peptide-membrane interactions
Peptides
Viral fusion inhibitors
Journal
Biochimica et biophysica acta. Biomembranes
ISSN: 1879-2642
Titre abrégé: Biochim Biophys Acta Biomembr
Pays: Netherlands
ID NLM: 101731713
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
received:
20
04
2021
revised:
20
08
2021
accepted:
25
08
2021
pubmed:
4
9
2021
medline:
4
1
2022
entrez:
3
9
2021
Statut:
ppublish
Résumé
Influenza viruses are major human pathogens, responsible for respiratory diseases affecting millions of people worldwide, with high morbidity and significant mortality. Infections by influenza can be controlled by vaccines and antiviral drugs. However, this virus is constantly under mutations, limiting the effectiveness of these clinical antiviral strategies. It is therefore urgent to develop new ones. Influenza hemagglutinin (HA) is involved in receptor binding and promotes the pH-dependent fusion of viral and cell endocytic membranes. HA-targeted peptides may emerge as a novel antiviral option to block this viral entry step. In this study, we evaluated three HA-derived (lipo)peptides using fluorescence spectroscopy. Peptide membrane interaction assays were performed at neutral and acidic pH to better resemble the natural conditions in which influenza fusion occurs. We found that peptide affinity towards membranes decreases upon the acidification of the environment. Therefore, the released peptides would be able to bind their complementary domain and interfere with the six-helix bundle formation necessary for viral fusion, and thus for the infection of the target cell. Our results provide new insight into molecular interactions between HA-derived peptides and cell membranes, which may contribute to the development of new influenza virus inhibitors.
Identifiants
pubmed: 34478733
pii: S0005-2736(21)00210-8
doi: 10.1016/j.bbamem.2021.183762
pmc: PMC9166161
mid: NIHMS1812533
pii:
doi:
Substances chimiques
Hemagglutinin Glycoproteins, Influenza Virus
0
Lipopeptides
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
183762Subventions
Organisme : NIAID NIH HHS
ID : R01 AI119762
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121349
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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