The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
The N501Y spike substitution enhances SARS-CoV-2 infection and transmission
Open accessAbstract
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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Cites
A pneumonia outbreak associated with a new coronavirus of probable bat origin
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Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England
The COVID-19 Genomics UK (COG-UK) consortium, Volz, E., Mishra, S., Chand, M., Barrett, J. C., Johnson, R., Geidelberg, L., Hinsley, W. R., Laydon, D. J., Dabrera, G., et al. (2021) · Nature · doi:10.1038/s41586-021-03470-x · Cited by 1,611
Spike mutation D614G alters SARS-CoV-2 fitness
Plante, J. A., Liu, Y., Liu, J., Xia, H., Johnson, B. A., Lokugamage, K. G., Zhang, X., Muruato, A. E., Zou, J., Fontes-Garfias, C. R., et al. (2021) · Nature · doi:10.1038/s41586-020-2895-3 · Cited by 1,558
Self-citationChan, J. F.-W., Zhang, A. J., Yuan, S., Poon, V. K.-M., Chan, C. C.-S., Lee, A. C.-Y., Chan, W.-M., Fan, Z., Tsoi, H.-W., Wen, L., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa325 · Cited by 1,058
SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo
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The biological and clinical significance of emerging SARS-CoV-2 variants
Tao, K., Tzou, P. L., Nouhin, J., Gupta, R. K., de Oliveira, T., Kosakovsky Pond, S. L., Fera, D., & Shafer, R. W. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00408-x · Cited by 1,009
Lamers, M. M., & Haagmans, B. L. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00713-0 · Cited by 983
Kurhade, C., Zou, J., Xia, H., Liu, M., Chang, H. C., Ren, P., Xie, X., & Shi, P. (2023) · Nature Medicine · doi:10.1038/s41591-022-02162-x · Cited by 423
Self-citationBNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants
Liu, J., Liu, Y., Xia, H., Zou, J., Weaver, S. C., Swanson, K. A., Cai, H., Cutler, M., Cooper, D., Muik, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03693-y · Cited by 342
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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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- 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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