Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation
Abstract
SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.
- Authors:
-
[1];
[1];
[4]
- Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
- Emory Univ., Atlanta, GA (United States). School of Medicine
- Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
- Fred Hutchinson Cancer Research Center, Seattle, WA (United States); National Inst. of Health, Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases (NIAID)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- Fred Hutch COVID-19 Research Fund; USDOE Office of Science (SC), Biological and Environmental Research (BER); Emory EVPHA Synergy Fund; Center for Childhood Infections and Vaccines; Children’s Healthcare of Atlanta; Woodruff Health Sciences Center; Emory School of Medicine
- OSTI Identifier:
- 1691536
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; SARS-CoV-2; Viral infection; X-ray crystallography
Citation Formats
Hurlburt, Nicholas K., Seydoux, Emilie, Wan, Yu-Hsin, Edara, Venkata Viswanadh, Stuart, Andrew B., Feng, Junli, Suthar, Mehul S., McGuire, Andrew T., Stamatatos, Leonidas, and Pancera, Marie. Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation. United States: N. p., 2020.
Web. doi:10.1038/s41467-020-19231-9.
Hurlburt, Nicholas K., Seydoux, Emilie, Wan, Yu-Hsin, Edara, Venkata Viswanadh, Stuart, Andrew B., Feng, Junli, Suthar, Mehul S., McGuire, Andrew T., Stamatatos, Leonidas, & Pancera, Marie. Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation. United States. https://doi.org/10.1038/s41467-020-19231-9
Hurlburt, Nicholas K., Seydoux, Emilie, Wan, Yu-Hsin, Edara, Venkata Viswanadh, Stuart, Andrew B., Feng, Junli, Suthar, Mehul S., McGuire, Andrew T., Stamatatos, Leonidas, and Pancera, Marie. Tue .
"Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation". United States. https://doi.org/10.1038/s41467-020-19231-9. https://www.osti.gov/servlets/purl/1691536.
@article{osti_1691536,
title = {Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation},
author = {Hurlburt, Nicholas K. and Seydoux, Emilie and Wan, Yu-Hsin and Edara, Venkata Viswanadh and Stuart, Andrew B. and Feng, Junli and Suthar, Mehul S. and McGuire, Andrew T. and Stamatatos, Leonidas and Pancera, Marie},
abstractNote = {SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.},
doi = {10.1038/s41467-020-19231-9},
journal = {Nature Communications},
number = 1,
volume = 11,
place = {United States},
year = {Tue Oct 27 00:00:00 EDT 2020},
month = {Tue Oct 27 00:00:00 EDT 2020}
}
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