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The N501Y spike substitution enhances SARS-CoV-2 transmission
Open accessAbstract
Summary: Beginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom (UK). This B.1.1.7 variant increased rapidly in prevalence among sequenced strains, attributed to an increase in infection and/or transmission efficiency. The UK variant has 19 nonsynonymous mutations across its viral genome including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 UK spike mutations, suggesting it is a major determinant responsible for increased transmission of this variant. Mechanistically, the N501Y substitution improved the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil and South Africa, our results indicate that N501Y substitution is a major adaptive spike mutation of major concern.
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“N501Y increases ACE2 affinity 128,146,147 and increases virus replication in human upper-airway cells and in the upper respiratory tracts of hamsters 127”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [127]
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Metadata
- Authors
- Liu, Y., Liu, J., Plante, K. S., Plante, J. A., Xie, X., Zhang, X., Ku, Z., An, Z., Scharton, D., Schindewolf, C., Menachery, V. D., Shi, P.-Y., & Weaver, S. C.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Corresponding author
- Shi, Pei-Yong
- Weaver, Scott C.
- ORCID
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2021-03-09
- Volume
- 602
- Issue
- 7896
- Pages
- 294-299
- ISSN
- 0028-0836 (ISSN-L)
- PMC
- PMC8900207
- OpenAlex
- W3216019834
- Cited by
- 574
- References
- 37
- Citations by year
- 2026: 25 · 2025: 71 · 2024: 84 · 2023: 125 · 2022: 181 · 2021: 87
- FWCI
- 37.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas (RP150551, RP150551 and RP190561, RP190561, AI153602)
- University of Texas System
- National Institutes of Health (AG049042, UL1TR001439)
- National Institute on Aging (AG049042)
- National Institute of Allergy and Infectious Diseases (R24AI120942, R01AI134907, R01AI153602, AI153602, AG049042, AI134907, T32AI007526)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- SARS-CoV-2, N501Y mutation, spike protein, B.1.1.7 Alpha variant, virus transmission, viral fitness, receptor binding affinity, airway epithelial cells, hamster model, convergent evolution, COVID-19 pandemic
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