Abstract |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells is a complex process that involves (1) recognition of the host entry receptor, angiotensin-converting enzyme 2 (ACE2), by the SARS-CoV-2 spike protein receptor binding domain (RBD), and (2) the subsequent fusion of the viral and cell membranes. Our long-term immune-defense is the production of antibodies (Abs) that recognize the SARS-CoV-2 RBD and successfully block viral infection. Thus, to understand immunity against SARS-CoV-2, a comprehensive molecular understanding of how human SARS-CoV-2 Abs recognize the RBD is needed. Here, we report the sequence-specific backbone assignment of the SARS-CoV-2 RBD and, furthermore, demonstrate that biomolecular NMR spectroscopy chemical shift perturbation (CSP) mapping successfully and rapidly identifies the molecular epitopes of RBD-specific mAbs. By incorporating NMR-based CSP mapping with other molecular techniques to define RBD-mAb interactions and then correlating these data with neutralization efficacy, structure-based approaches for developing improved vaccines and COVID-19 mAb-based therapies will be greatly accelerated.
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Authors | Marta V Schoenle, Yang Li, Meng Yuan, Michael W Clarkson, Ian A Wilson, Wolfgang Peti, Rebecca Page |
Journal | Journal of the American Chemical Society
(J Am Chem Soc)
Vol. 143
Issue 21
Pg. 7930-7934
(06 02 2021)
ISSN: 1520-5126 [Electronic] United States |
PMID | 34018723
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Viral
- Epitopes
- Spike Glycoprotein, Coronavirus
- spike protein, SARS-CoV-2
- Angiotensin-Converting Enzyme 2
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Topics |
- Amino Acid Sequence
- Angiotensin-Converting Enzyme 2
(chemistry, metabolism)
- Antibodies, Monoclonal
(chemistry, metabolism)
- Antibodies, Viral
(chemistry, metabolism)
- Binding Sites
- COVID-19
(metabolism)
- Epitopes
(chemistry)
- Humans
- Nuclear Magnetic Resonance, Biomolecular
- Protein Binding
- Protein Domains
- SARS-CoV-2
(metabolism)
- Spike Glycoprotein, Coronavirus
(chemistry, metabolism)
- Structure-Activity Relationship
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