ArticlebioRxiv : the preprint server for biology2023
Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning.
Ruipeng Lei, Enya Qing, Abby Odle, Meng Yuan, Timothy J C Tan, Natalie So, Wenhao O Ouyang, Ian A Wilson, Tom Gallagher, Stanley Perlman and 2 more
Open access · greenAbstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
12 authors at 5 institutions in 1 country.
Ruipeng LeiDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Enya QingDepartment of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153, USA.
Abby OdleDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA.
Meng YuanDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-9754-4503 Timothy J C TanCenter for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.ORCID 0000-0001-5337-5357 Natalie SoDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Wenhao O OuyangDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.ORCID 0000-0002-3618-9808 Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Tom GallagherDepartment of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153, USA.
Stanley PerlmanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA.
Nicholas C WuDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.ORCID 0000-0002-9078-6697 Lok-Yin Roy WongDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA.ORCID 0000-0002-0727-8289 University of Illinois Urbana-Champaign · USLoyola University Chicago · USScripps Research Institute · USUniversity of Iowa · USRutgers, The State University of New Jersey · US
Funding
SARS-CoV Proteins in Heterologous Viral InfectionP01AI060699 · NIAID · UNIVERSITY OF IOWA · PI GALLAGHER, THOMAS MILLER · 2004 to 2021
$21.5MRole of eicosanoids in pathogenic human CoV infectionsR01AI129269 · NIAID · UNIVERSITY OF IOWA · PI Stanley Perlman · 2016 to 2026
$4.7MImpacts of Adaptive Coronavirus Evolution on Viral Membrane FusionR21AI178391 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI GALLAGHER, THOMAS MILLER · 2023 to 2024
$437kPhenotypic and functional characterization of Betacoronavirus Internal protein in relation to virulenceK99AI170996 · NIAID · UNIVERSITY OF IOWA · PI WONG, LOK-YIN ROY · 2022 to 2023
$181kNIAID NIH HHS K99 AI170996NIAID NIH HHS P01 AI060699NIAID NIH HHS R01 AI129269NIAID NIH HHS R21 AI178391
6 · The paper itselfAbstract
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 performed 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 identified mutations at residue 813 of the spike protein that reduced TMPRSS2-mediated entry with decreased virulence. In addition, we showed 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.
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PMID38076875
PMCPMC10705381
OpenAlexW4389119356
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