Journal article
Dual-role epitope on SARS-CoV-2 spike enhances and neutralizes viral entry across different variants
PLoS pathogens, Vol.20(9), e1012493
09/05/2024
DOI: 10.1371/journal.ppat.1012493
PMCID: PMC11407660
PMID: 39236072
Abstract
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 enhances 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.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 enhances 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.
Details
- Title: Subtitle
- Dual-role epitope on SARS-CoV-2 spike enhances and neutralizes viral entry across different variants
- Creators
- Gang Ye - University of Minnesota Medical CenterFan Bu - University of Minnesota Medical CenterRuangang PanAlise Mendoza - University of Minnesota Medical CenterDivyasha Saxena - University of LouisvilleJian Zheng - University of LouisvilleStanley Perlman - University of IowaBin Liu - HormelFang Li - University of Minnesota
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.20(9), e1012493
- Publisher
- PUBLIC LIBRARY SCIENCE
- DOI
- 10.1371/journal.ppat.1012493
- PMID
- 39236072
- PMCID
- PMC11407660
- ISSN
- 1553-7374
- eISSN
- 1553-7374
- Grant note
- NIH: R01AI089728, R01AI110700, R01AI157975, U19AI171954
This study was supported by funding from NIH grants R01AI089728 (to F.L.), R01AI110700(to F.L.), R01AI157975 (to F.L.), and U19AI171954 (to F.L., S.P., B.L.).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Language
- English
- Date published
- 09/05/2024
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984701756602771
Metrics
4 Record Views