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

Yang Liu, Jianying Liu, Kenneth S. Plante, Jessica A. Plante, Xuping Xie, Xianwen Zhang, Zhiqiang Ku, Zhiqiang An, Dionna Scharton, Craig Schindewolf, Steven G. Widen, Vineet D. Menachery, Pei-Yong Shi () and Scott C. Weaver ()
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Yang Liu: University of Texas Medical Branch
Jianying Liu: University of Texas Medical Branch
Kenneth S. Plante: University of Texas Medical Branch
Jessica A. Plante: University of Texas Medical Branch
Xuping Xie: University of Texas Medical Branch
Xianwen Zhang: University of Texas Medical Branch
Zhiqiang Ku: The University of Texas Health Science Center at Houston
Zhiqiang An: The University of Texas Health Science Center at Houston
Dionna Scharton: University of Texas Medical Branch
Craig Schindewolf: University of Texas Medical Branch
Steven G. Widen: University of Texas Medical Branch
Vineet D. Menachery: University of Texas Medical Branch
Pei-Yong Shi: University of Texas Medical Branch
Scott C. Weaver: University of Texas Medical Branch

Nature, 2022, vol. 602, issue 7896, 294-299

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41586-021-04245-0

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