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TitleDual-role epitope on SARS-CoV-2 spike enhances and neutralizes viral entry across different variants.
Journal, issue, pagesPLoS Pathog, Vol. 20, Issue 9, Page e1012493, Year 2024
Publish dateSep 5, 2024
AuthorsGang Ye / Fan Bu / Ruangang Pan / Alise Mendoza / Divyasha Saxena / Jian Zheng / Stanley Perlman / Bin Liu / Fang Li /
PubMed AbstractGrasping the roles of epitopes in viral glycoproteins is essential for unraveling the structure and function of these proteins. Up to now, all identified epitopes have been found to either ...Grasping the roles of epitopes in viral glycoproteins is essential for unraveling the structure and function of these proteins. Up to now, all identified epitopes have been found to either neutralize, have no effect on, or enhance viral entry into cells. Here, we used nanobodies (single-domain antibodies) as probes to investigate a unique epitope on the SARS-CoV-2 spike protein, located outside the protein's receptor-binding domain. Nanobody binding to this epitope enhances the cell entry of prototypic SARS-CoV-2, while neutralizing the cell entry of SARS-CoV-2 Omicron variant. Moreover, nanobody binding to this epitope promotes both receptor binding activity and post-attachment activity of prototypic spike, explaining the enhanced viral entry. The opposite occurs with Omicron spike, explaining the neutralized viral entry. This study reveals a unique epitope that can both enhance and neutralize viral entry across distinct viral variants, suggesting that epitopes may vary their roles depending on the viral context. Consequently, antibody therapies should be assessed across different viral variants to confirm their efficacy and safety.
External linksPLoS Pathog / PubMed:39236072 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.8 Å
Structure data

29798

8g76

EMDB-29798, PDB-8g76:
SARS-CoV-2 spike/Nb5 complex
Method: EM (single particle) / Resolution: 3.8 Å

29799

8g77

EMDB-29799, PDB-8g77:
SARS-CoV-2 spike/Nb6 complex
Method: EM (single particle) / Resolution: 2.8 Å

42218

8ug9

EMDB-42218, PDB-8ug9:
XBB.1.5 spike/Nb5 complex
Method: EM (single particle) / Resolution: 3.49 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • vicugna pacos (alpaca)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / VIRAL PROTEIN-IMMUNE SYSTEM complex / Nanobody / XBB.1.5

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