The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
SARS-CoV-2 RBD in vitro evolution follows contagious mutation spread, yet generates an able infection inhibitor
Open accessPreprint — published as 10.1038/s41564-021-00954-4
Abstract
SARS-CoV-2 is continually evolving, with more contagious mutations spreading rapidly. Using in vitro evolution to affinity maturate the receptor-binding domain (RBD) of the spike protein towards ACE2 resulted in the more contagious mutations, S477N, E484K, and N501Y, to be among the first selected, explaining the convergent evolution of the “European” (20E-EU1), “British” (501.V1),”South African” (501.V2), and ‘‘Brazilian” variants (501.V3). Plotting the binding affinity to ACE2 of all RBD mutations against their incidence in the population shows a strong correlation between the two. Further in vitro evolution enhancing binding by 600-fold provides guidelines towards potentially new evolving mutations with even higher infectivity. For example, Q498R epistatic to N501Y. Nevertheless, the high-affinity RBD is also an efficient drug, inhibiting SARS-CoV-2 infection. The 2.9Å Cryo-EM structure of the high-affinity complex, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.
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“The RBD mutation N501Y, which increases affinity to ACE2 and is present in B.1.1.7 and B.1.351(ref.20 ), does not impair on its own post-vaccine serum neutralization 21 .”
From Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies (2021) · cites this paper as [20]
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UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 46,047
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286
MolProbity : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination
Punjani, A., Rubinstein, J. L., Fleet, D. J., & Brubaker, M. A. (2017) · Nature Methods · doi:10.1038/nmeth.4169 · Cited by 11,626
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020) · Science · doi:10.1126/science.abb2507 · Cited by 8,897
Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein
Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586
Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
Lan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., et al. (2020) · Nature · doi:10.1038/s41586-020-2180-5 · Cited by 5,983
Automated electron microscope tomography using robust prediction of specimen movements
Mastronarde, D. N. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.07.007 · Cited by 5,136
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Lopez, E., Barthelemy, M., Baronti, C., et al. (2021) · medRxiv · doi:10.1101/2021.06.16.21259035
Alpha variant versus D614G strain in the Syrian hamster modelPreprint
Cochin, M., Lucıanı, L., Touret, F., Driouich, J., Petit, P.-R., Moureau, G., Baronti, C., Laprie, C., Thirion, L., Maes, P., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.19.440435
Metadata
- Authors
- Zahradník, J., Marciano, S., Shemesh, M., Zoler, E., Chiaravalli, J., Meyer, B., Rudich, Y., Dym, O., Elad, N., & Schreiber, G.
- Affiliations
- Weizmann Institute of Science (IL)
- Institut Pasteur (FR)
- Corresponding author
- Schreiber, Gideon
- ORCID
- Venue
- Nature Microbiology
- Publisher
- openRxiv
- Published
- 2021-01-06
- Volume
- 6
- Issue
- 9
- Pages
- 1188-1198
- ISSN
- 2058-5276 (ISSN-L)
- OpenAlex
- W3193682077
- Cited by
- 458
- References
- 0
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 42 · 2023: 82 · 2022: 177 · 2021: 103
- FWCI
- 32.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Microbiology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (acceptedVersion, cc-by)
- HAL (submittedVersion)
- Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Weizmann Institute of Science
- Israel Science Foundation (3814/19)
- Nature
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, spike protein receptor-binding domain, ACE2 binding affinity, in vitro evolution, affinity maturation, SARS-CoV-2 variants, E484K, N501Y, antiviral drug design, hamster challenge model, COVID-19 pandemic, vaccine development
- MeSH terms
- Protein Domains, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Animals, Antiviral Agents, Female, Cricetinae, Humans, Male, Mesocricetus, Mutation, Protein Binding, Receptors, Virus, Drug Design, Evolution, Molecular, Virus Internalization, Molecular Dynamics Simulation, Spike Glycoprotein, Coronavirus
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