Fiche publication
Date publication
octobre 2022
Journal
International journal of biological macromolecules
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak
Tous les auteurs :
Cano-Muñoz M, Polo-Megías D, Cámara-Artigas A, Gavira JA, López-Rodríguez MJ, Laumond G, Schmidt S, Demiselle J, Bahram S, Moog C, Conejero-Lara F
Lien Pubmed
Résumé
SARS-CoV-2 spike (S) protein mediates virus attachment to the cells and fusion between viral and cell membranes. Membrane fusion is driven by mutual interaction between the highly conserved heptad-repeat regions 1 and 2 (HR1 and HR2) of the S2 subunit of the spike. For this reason, these S2 regions are interesting therapeutic targets for COVID-19. Although HR1 and HR2 have been described as transiently exposed during the fusion process, no significant antibody responses against these S2 regions have been reported. Here we designed chimeric proteins that imitate highly stable HR1 helical trimers and strongly bind to HR2. The proteins have broad inhibitory activity against WT B.1 and BA.1 viruses. Sera from COVID-19 convalescent donors showed significant levels of reactive antibodies (IgG and IgA) against the HR1 mimetic proteins, whereas these antibody responses were absent in sera from uninfected donors. Moreover, both inhibitory activity and antigenicity of the proteins correlate positively with their structural stability but not with the number of amino acid changes in their HR1 sequences, indicating a conformational and conserved nature of the involved epitopes. Our results reveal previously undetected spike epitopes that may guide the design of new robust COVID-19 vaccines and therapies.
Mots clés
COVID-19, Fusion inhibitor, Vaccine
Référence
Int J Biol Macromol. 2022 10 8;:
