The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets
Open accessAbstract
SARS-CoV-2 entry requires sequential cleavage of the spike glycoprotein at the S1/S2 and the S2ʹ cleavage sites to mediate membrane fusion. SARS-CoV-2 has a polybasic insertion (PRRAR) at the S1/S2 cleavage site that can be cleaved by furin. Using lentiviral pseudotypes and a cell-culture-adapted SARS-CoV-2 virus with an S1/S2 deletion, we show that the polybasic insertion endows SARS-CoV-2 with a selective advantage in lung cells and primary human airway epithelial cells, but impairs replication in Vero E6, a cell line used for passaging SARS-CoV-2. Using engineered spike variants and live virus competition assays and by measuring growth kinetics, we find that the selective advantage in lung and primary human airway epithelial cells depends on the expression of the cell surface protease TMPRSS2, which enables endosome-independent virus entry by a route that avoids antiviral IFITM proteins. SARS-CoV-2 virus lacking the S1/S2 furin cleavage site was shed to lower titres from infected ferrets and was not transmitted to cohoused sentinel animals, unlike wild-type virus. Analysis of 100,000 SARS-CoV-2 sequences derived from patients and 24 human postmortem tissues showed low frequencies of naturally occurring mutants that harbour deletions at the polybasic site. Taken together, our findings reveal that the furin cleavage site is an important determinant of SARS-CoV-2 transmission. Efficient transmission of SARS-CoV-2 among infected ferrets requires a functional furin cleavage site in the SARS-CoV-2 spike protein.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A novel coronavirus from patients with pneumonia in China, 2019
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001017 · Cited by 28,244
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2012-7 · Cited by 21,969
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
First case of 2019 novel coronavirus in the United States
Holshue, M. L., DeBolt, C., Lindquist, S., Lofy, K. H., Wiesman, J., Bruce, H., Spitters, C., Ericson, K., Wilkerson, S., Tural, A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001191 · Cited by 6,030
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923
The proximal origin of SARS-CoV-2
Andersen, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C., & Garry, R. F. (2020) · Nature Medicine · doi:10.1038/s41591-020-0820-9 · Cited by 5,081
Cell entry mechanisms of SARS-CoV-2
Shang, J., Wan, Y., Luo, C., Ye, G., Geng, Q., Auerbach, A., & Li, F. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003138117 · Cited by 3,142
Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche
Kärber, G. (1931) · Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie · doi:10.1007/bf01863914 · Cited by 3,104
Ou, X., Liu, Y., Lei, X., Li, P., Mi, D., Ren, L., Guo, L., Guo, R., Chen, T., Hu, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15562-9 · Cited by 3,097
Hoffmann, M., Kleine-Weber, H., & Pöhlmann, S. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.022 · Cited by 1,852
Cited by
Mechanisms of SARS-CoV-2 entry into cells
Jackson, C. B., Farzan, M., Chen, B., & Choe, H. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00418-x · Cited by 3,022
Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England
Davies, N. G., Abbott, S., Barnard, R. C., Jarvis, C. I., Kucharski, A. J., Munday, J. D., Pearson, C. A. B., Russell, T. W., Tully, D. C., Washburne, A. D., et al. (2021) · Science · doi:10.1126/science.abg3055 · Cited by 2,581
SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
Mlcochova, P., Kemp, S. A., Dhar, M. S., Papa, G., Meng, B., Ferreira, I. A. T. M., Datir, R., Collier, D. A., Albecka, A., Singh, S., et al. (2021) · Nature · doi:10.1038/s41586-021-03944-y · Cited by 1,337
Self-citationMarkov, P. V., Ghafari, M., Beer, M., Lythgoe, K., Simmonds, P., Stilianakis, N. I., & Katzourakis, A. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-023-00878-2 · Cited by 1,179
Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity
Meng, B., Abdullahi, A., Ferreira, I. A. T. M., Goonawardane, N., Saito, A., Kimura, I., Yamasoba, D., Gerber, P. P., Fatihi, S., Rathore, S., et al. (2022) · Nature · doi:10.1038/s41586-022-04474-x · Cited by 1,146
Metadata
- Authors
- Peacock, T. P., Goldhill, D. H., Zhou, J., Baillon, L., Frise, R., Swann, O. C., Kugathasan, R., Penn, R., Brown, J. C., Sanchez-David, R. Y., Braga, L., Williamson, M. K., Hassard, J. A., Staller, E., Hanley, B., Osborn, M., Giacca, M., Davidson, A. D., Matthews, D. A., & Barclay, W. S.
- Venue
- Nature Microbiology
- Published
- 2021-04-27
- Volume
- 6
- Issue
- 7
- Pages
- 899-909
- ISSN
- 2058-5276 (ISSN-L)
- OpenAlex
- W3159140204
- Cited by
- 731
- References
- 67
- FWCI
- 45.46
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. https://app.cochat.ai/papers/10.1038/s41564-021-00908-w
- The paper
- Peacock, T. P., Goldhill, D. H., Zhou, J., Baillon, L., Frise, R., Swann, O. C., Kugathasan, R., Penn, R., Brown, J. C., Sanchez-David, R. Y., Braga, L., Williamson, M. K., Hassard, J. A., Staller, E., Hanley, B., Osborn, M., Giacca, M., Davidson, A. D., Matthews, D. A., & Barclay, W. S. (2021). The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nature Microbiology. https://doi.org/10.1038/s41564-021-00908-w
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
