Journal article
Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning
Nature communications, Vol.15(1), 4056
05/14/2024
DOI: 10.1038/s41467-024-48104-8
PMCID: PMC11094058
PMID: 38744813
Abstract
The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane fusion during virus entry and is part of a broadly neutralizing epitope. However, sequence determinants at the fusion peptide and its adjacent regions for pathogenicity and antigenicity remain elusive. In this study, we perform a series of deep mutational scanning (DMS) experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 in different cell lines and in the presence of broadly neutralizing antibodies. We identify mutations at residue 813 of the spike protein that reduced TMPRSS2-mediated entry with decreased virulence. In addition, we show that an F823Y mutation, present in bat betacoronavirus HKU9 spike protein, confers resistance to broadly neutralizing antibodies. Our findings provide mechanistic insights into SARS-CoV-2 pathogenicity and also highlight a potential challenge in developing broadly protective S2-based coronavirus vaccines.Deep mutational scanning experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 with different cell lines revealed that mutations at residue 813 of the spike protein reduced TMPRSS2-mediated entry with decreased virulence.
Details
- Title: Subtitle
- Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning
- Creators
- Ruipeng Lei - University of Illinois Urbana-ChampaignEnya Qing - Loyola University ChicagoAbby Odle - University of IowaMeng Yuan - Scripps Research InstituteChaminda D Gunawardene - Rutgers, The State University of New JerseyTimothy J. C Tan - University of Illinois Urbana-ChampaignNatalie So - University of Illinois Urbana-ChampaignWenhao O Ouyang - University of Illinois Urbana-ChampaignIan A Wilson - Scripps Research InstituteTom Gallagher - Loyola University ChicagoStanley Perlman - University of IowaNicholas C Wu - University of Illinois Urbana-ChampaignLok-Yin Roy Wong - Rutgers, The State University of New Jersey
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.15(1), 4056
- DOI
- 10.1038/s41467-024-48104-8
- PMID
- 38744813
- PMCID
- PMC11094058
- NLM abbreviation
- Nat Commun
- eISSN
- 2041-1723
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 05/14/2024
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984627149702771
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