eLife (Mar 2023)
Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses
- Rui P Silva,
- Yimin Huang,
- Annalee W Nguyen,
- Ching-Lin Hsieh,
- Oladimeji S Olaluwoye,
- Tamer S Kaoud,
- Rebecca E Wilen,
- Ahlam N Qerqez,
- Jun-Gyu Park,
- Ahmed M Khalil,
- Laura R Azouz,
- Kevin C Le,
- Amanda L Bohanon,
- Andrea M DiVenere,
- Yutong Liu,
- Alison G Lee,
- Dzifa A Amengor,
- Sophie R Shoemaker,
- Shawn M Costello,
- Eduardo A Padlan,
- Susan Marqusee,
- Luis Martinez-Sobrido,
- Kevin N Dalby,
- Sheena D'Arcy,
- Jason S McLellan,
- Jennifer A Maynard
Affiliations
- Rui P Silva
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
- Yimin Huang
- ORCiD
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
- Annalee W Nguyen
- ORCiD
- Department of Chemical Engineering, The University of Texas at Austin, Austin, United States
- Ching-Lin Hsieh
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
- Oladimeji S Olaluwoye
- ORCiD
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Dallas, United States
- Tamer S Kaoud
- ORCiD
- Division of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, United States
- Rebecca E Wilen
- Department of Chemical Engineering, The University of Texas at Austin, Austin, United States
- Ahlam N Qerqez
- Department of Chemical Engineering, The University of Texas at Austin, Austin, United States
- Jun-Gyu Park
- Texas Biomedical Research Institute, San Antonio, United States; Laboratory of Veterinary Zoonosis, College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea
- Ahmed M Khalil
- Texas Biomedical Research Institute, San Antonio, United States
- Laura R Azouz
- Department of Chemical Engineering, The University of Texas at Austin, Austin, United States
- Kevin C Le
- ORCiD
- Department of Chemical Engineering, The University of Texas at Austin, Austin, United States
- Amanda L Bohanon
- ORCiD
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
- Andrea M DiVenere
- Department of Chemical Engineering, The University of Texas at Austin, Austin, United States
- Yutong Liu
- Department of Chemical Engineering, The University of Texas at Austin, Austin, United States
- Alison G Lee
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
- Dzifa A Amengor
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
- Sophie R Shoemaker
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
- Shawn M Costello
- Biophysics Graduate Program, University of California, Berkeley, Berkeley, United States
- Eduardo A Padlan
- Retired, Kensington, United States
- Susan Marqusee
- ORCiD
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Department of Chemistry, University of California, Berkeley, Berkeley, United States
- Luis Martinez-Sobrido
- Texas Biomedical Research Institute, San Antonio, United States
- Kevin N Dalby
- ORCiD
- Division of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, United States
- Sheena D'Arcy
- ORCiD
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Dallas, United States
- Jason S McLellan
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States; LaMontagne Center for Infectious Diseases, The University of Texas at Austin, Austin, United States
- Jennifer A Maynard
- ORCiD
- Department of Chemical Engineering, The University of Texas at Austin, Austin, United States; LaMontagne Center for Infectious Diseases, The University of Texas at Austin, Austin, United States
- DOI
- https://doi.org/10.7554/eLife.83710
- Journal volume & issue
-
Vol. 12
Abstract
To address the ongoing SARS-CoV-2 pandemic and prepare for future coronavirus outbreaks, understanding the protective potential of epitopes conserved across SARS-CoV-2 variants and coronavirus lineages is essential. We describe a highly conserved, conformational S2 domain epitope present only in the prefusion core of β-coronaviruses: SARS-CoV-2 S2 apex residues 980–1006 in the flexible hinge. Antibody RAY53 binds the native hinge in MERS-CoV and SARS-CoV-2 spikes on the surface of mammalian cells and mediates antibody-dependent cellular phagocytosis and cytotoxicity against SARS-CoV-2 spike in vitro. Hinge epitope mutations that ablate antibody binding compromise pseudovirus infectivity, but changes elsewhere that affect spike opening dynamics, including those found in Omicron BA.1, occlude the epitope and may evade pre-existing serum antibodies targeting the S2 core. This work defines a third class of S2 antibody while providing insights into the potency and limitations of S2 core epitope targeting.
Keywords
