tetano
Editor, Senior Moderator
J Am Chem Soc
. 2021 May 21.
doi: 10.1021/jacs.1c03945. Online ahead of print.
NMR Based SARS-CoV-2 Antibody Screening
Marta V Schoenle[SUP] 1 [/SUP], Yang Li[SUP] 2 [/SUP], Meng Yuan[SUP] 3 [/SUP], Michael W Clarkson[SUP] 4 [/SUP], Ian A Wilson[SUP] 3 5 [/SUP], Wolfgang Peti[SUP] 2 [/SUP], Rebecca Page[SUP] 6 [/SUP]
Affiliations
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.
. 2021 May 21.
doi: 10.1021/jacs.1c03945. Online ahead of print.
NMR Based SARS-CoV-2 Antibody Screening
Marta V Schoenle[SUP] 1 [/SUP], Yang Li[SUP] 2 [/SUP], Meng Yuan[SUP] 3 [/SUP], Michael W Clarkson[SUP] 4 [/SUP], Ian A Wilson[SUP] 3 5 [/SUP], Wolfgang Peti[SUP] 2 [/SUP], Rebecca Page[SUP] 6 [/SUP]
Affiliations
- PMID: 34018723
- DOI: 10.1021/jacs.1c03945
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.