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The N501Y spike substitution enhances SARS-CoV-2 infection and transmission

Open access
Liu, Yang, Liu, Jianying, Plante, Kenneth S., Plante, Jessica A., Xie, Xuping, Zhang, Xianwen, Ku, Zhiqiang, An, Zhiqiang, Scharton, Dionna, Schindewolf, Craig, Widen, Steven G., Menachery, Vineet D., Shi, Pei-Yong, Weaver, Scott C.·2022·Nature

Abstract

The B.1.1.7 variant (also known as Alpha) of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the UK in the summer of 2020. The prevalence of this variant increased rapidly owing to an increase in infection and/or transmission efficiency1. The Alpha variant contains 19 nonsynonymous mutations across its viral genome, including 8 substitutions or deletions in the spike protein that 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 resulted in consistent fitness gains for replication in the upper airway in a hamster model as well as in primary human airway epithelial cells. The N501Y substitution recapitulated the enhanced viral transmission phenotype of the eight mutations in the Alpha spike protein, suggesting that it is a major determinant of the increased transmission of the Alpha variant. Mechanistically, the N501Y substitution increased the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil, South Africa and elsewhere2,3, our results indicate that N501Y substitution is an adaptive spike mutation of major concern. Experiments in a hamster model of COVID-19 and human airway epithelial cells show that the spike N501Y mutation is the major determinant of increased fitness of the B.1.1.7 Alpha variant of SARS-CoV-2.

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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., Widen, S. G., Menachery, V. D., Shi, P.-Y., & Weaver, S. C.
Venue
Nature
Published
2021-11-24
Volume
602
Issue
7896
Pages
294-299
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W3216019834
Cited by
572
References
35
FWCI
35.31
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. https://app.cochat.ai/papers/10.1038/s41586-021-04245-0
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Liu, Y., Liu, J., Plante, K. S., Plante, J. A., Xie, X., Zhang, X., Ku, Z., An, Z., Scharton, D., Schindewolf, C., Widen, S. G., Menachery, V. D., Shi, P.-Y., & Weaver, S. C. (2022). The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. Nature. https://doi.org/10.1038/s41586-021-04245-0

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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