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Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies

View ORCID ProfileGabriele Cerutti, Micah Rapp, Yicheng Guo, Fabiana Bahna, Jude Bimela, Eswar R. Reddem, Jian Yu, Pengfei Wang, Lihong Liu, Yaoxing Huang, David D. Ho, Peter D. Kwong, Zizhang Sheng, Lawrence Shapiro
doi: https://doi.org/10.1101/2021.02.21.432168
Gabriele Cerutti
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
2Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10029, USA
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  • ORCID record for Gabriele Cerutti
Micah Rapp
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
2Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10029, USA
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Yicheng Guo
2Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10029, USA
3Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Fabiana Bahna
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
2Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10029, USA
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Jude Bimela
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
2Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10029, USA
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Eswar R. Reddem
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
2Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10029, USA
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Jian Yu
3Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Pengfei Wang
3Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Lihong Liu
3Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Yaoxing Huang
3Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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David D. Ho
3Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Peter D. Kwong
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
4Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Zizhang Sheng
3Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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  • For correspondence: zs2248@cumc.columbia.edu lss8@columbia.edu
Lawrence Shapiro
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
2Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10029, USA
3Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
4Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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  • For correspondence: zs2248@cumc.columbia.edu lss8@columbia.edu
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Summary

Emerging SARS-CoV-2 strains, B.1.1.7 and B.1.351, from the UK and South Africa, respectively show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against the original wild-type virus, and are thus of clinical concern. However, the neutralization potency of two antibodies, 1-57 and 2-7, which target the receptor-binding domain (RBD) of spike, was unaffected by these emerging strains. Here, we report cryo-EM structures of 1-57 and 2-7 in complex with spike, revealing each of these antibodies to utilize a distinct mechanism to bypass or accommodate RBD mutations. Notably, each antibody represented a response with recognition distinct from those of frequent antibody classes. Moreover, many epitope residues recognized by 1-57 and 2-7 were outside hotspots of evolutionary pressure for both ACE2 binding and neutralizing antibody escape. We suggest the therapeutic use of antibodies like 1-57 and 2-7, which target less prevalent epitopes, could ameliorate issues of monoclonal antibody escape.

Competing Interest Statement

DDH, YH, JY, LL and PW are inventors of a patent describing some of the antibodies reported on here.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 22, 2021.
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Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies
Gabriele Cerutti, Micah Rapp, Yicheng Guo, Fabiana Bahna, Jude Bimela, Eswar R. Reddem, Jian Yu, Pengfei Wang, Lihong Liu, Yaoxing Huang, David D. Ho, Peter D. Kwong, Zizhang Sheng, Lawrence Shapiro
bioRxiv 2021.02.21.432168; doi: https://doi.org/10.1101/2021.02.21.432168
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Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies
Gabriele Cerutti, Micah Rapp, Yicheng Guo, Fabiana Bahna, Jude Bimela, Eswar R. Reddem, Jian Yu, Pengfei Wang, Lihong Liu, Yaoxing Huang, David D. Ho, Peter D. Kwong, Zizhang Sheng, Lawrence Shapiro
bioRxiv 2021.02.21.432168; doi: https://doi.org/10.1101/2021.02.21.432168

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