Structural Dynamics of the SARS-CoV-2 Spike Protein: A 2-Year Retrospective Analysis of SARS-CoV-2 Variants (from Alpha to Omicron) Reveals an Early Divergence between Conserved and Variable Epitopes - Aix-Marseille Université Access content directly
Journal Articles Molecules Year : 2022

Structural Dynamics of the SARS-CoV-2 Spike Protein: A 2-Year Retrospective Analysis of SARS-CoV-2 Variants (from Alpha to Omicron) Reveals an Early Divergence between Conserved and Variable Epitopes

Patrick Guérin
  • Function : Author
Nouara Yahi
  • Function : Author
Fodil Azzaz
  • Function : Author
Henri Chahinian
  • Function : Author
Jean-Marc Sabatier
Jacques Fantini
  • Function : Author

Abstract

We analyzed the epitope evolution of the spike protein in 1,860,489 SARS-CoV-2 genomes. The structural dynamics of these epitopes was determined by molecular modeling approaches. The D614G mutation, selected in the first months of the pandemic, is still present in currently circulating SARS-CoV-2 strains. This mutation facilitates the conformational change leading to the demasking of the ACE2 binding domain. D614G also abrogated the binding of facilitating antibodies to a linear epitope common to SARS-CoV-1 and SARS-CoV-2. The main neutralizing epitope of the N-terminal domain (NTD) of the spike protein showed extensive structural variability in SARS-CoV-2 variants, especially Delta and Omicron. This epitope is located on the flat surface of the NTD, a large electropositive area which binds to electronegatively charged lipid rafts of host cells. A facilitating epitope located on the lower part of the NTD appeared to be highly conserved among most SARS-CoV-2 variants, which may represent a risk of antibody-dependent enhancement (ADE). Overall, this retrospective analysis revealed an early divergence between conserved (facilitating) and variable (neutralizing) epitopes of the spike protein. These data aid in the designing of new antiviral strategies that could help to control COVID-19 infection by mimicking neutralizing antibodies or by blocking facilitating antibodies.
Fichier principal
Vignette du fichier
molecules-27-03851.pdf (21.94 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Licence : CC BY - Attribution

Dates and versions

hal-03713875 , version 1 (02-10-2023)

Licence

Attribution

Identifiers

Cite

Patrick Guérin, Nouara Yahi, Fodil Azzaz, Henri Chahinian, Jean-Marc Sabatier, et al.. Structural Dynamics of the SARS-CoV-2 Spike Protein: A 2-Year Retrospective Analysis of SARS-CoV-2 Variants (from Alpha to Omicron) Reveals an Early Divergence between Conserved and Variable Epitopes. Molecules, 2022, 27 (12), pp.3851. ⟨10.3390/molecules27123851⟩. ⟨hal-03713875⟩
52 View
3 Download

Altmetric

Share

Gmail Facebook X LinkedIn More