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NMR Based SARS-CoV-2 Antibody Screening.

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.
AuthorsMarta V Schoenle, Yang Li, Meng Yuan, Michael W Clarkson, Ian A Wilson, Wolfgang Peti, Rebecca Page
JournalJournal 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
PMID34018723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Angiotensin-Converting Enzyme 2
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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