Neuropilin-1 is a host factor for SARS-CoV-2 infection
Open accessPublished version of a preprint
Abstract
Another host factor for SARS-CoV-2 Virus-host interactions determine cellular entry and spreading in tissues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the earlier SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as a receptor; however, their tissue tropism differs, raising the possibility that additional host factors are involved. The spike protein of SARS-CoV-2 contains a cleavage site for the protease furin that is absent from SARS-CoV (see the Perspective by Kielian). Cantuti-Castelvetri et al. now show that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial and epithelial cells. Daly et al. found that the furin-cleaved S1 fragment of the spike protein binds directly to cell surface NRP1 and blocking this interaction with a small-molecule inhibitor or monoclonal antibodies reduced viral infection in cell culture. Understanding the role of NRP1 in SARS-CoV-2 infection may suggest potential targets for future antiviral therapeutics. Science , this issue p. 856 , p. 861 ; see also p. 765
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
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The C-terminal motif of the cleaved S1 subunit can bind to neuropillin-1 (NRP-1), which negatively influences T cell memory.
“Interestingly, the C-terminal motif of the cleaved S1 subunit can bind to neuropillin-1 (NRP-1),67,68 which negatively influences T cell memory.69”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [68]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
U-Net: Convolutional Networks for Biomedical Image Segmentation
Ronneberger, O., Fischer, P., & Brox, T. (2015) · Lecture notes in computer science · doi:10.1007/978-3-319-24574-4_28 · Cited by 99,404 · see citing works
<i>PHENIX</i> : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716 · see citing works
<i>Phaser</i> crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · see citing works
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 · see citing works
Kabsch, W. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909047337 · Cited by 16,463 · see citing works
<i>MolProbity</i> : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115 · see citing works
An interactive web-based dashboard to track COVID-19 in real time
Dong, E., Du, H., & Gardner, L. (2020) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30120-1 · Cited by 10,048 · see citing works
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020) · Science · doi:10.1126/science.abb2507 · Cited by 8,897 · see citing works
Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein
Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586 · see citing works
Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19
Ackermann, M., Verleden, S. E., Kuehnel, M., Haverich, A., Welte, T., Laenger, F., Vanstapel, A., Werlein, C., Stark, H., Tzankov, A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2015432 · Cited by 5,613 · see citing works
How good are my data and what is the resolution?
Evans, P. R., & Murshudov, G. N. (2013) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444913000061 · Cited by 4,747 · see citing works
Dali server: conservation mapping in 3D
Holm, L., & Rosenstr�m, P. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq366 · Cited by 3,640 · see citing works
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 · see citing works
Hoffmann, M., Kleine-Weber, H., & Pöhlmann, S. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.022 · Cited by 1,852 · see citing works
Mechanisms and regulation of endothelial VEGF receptor signalling
Simons, M., Gordon, E., & Claesson-Welsh, L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.87 · Cited by 1,498 · see citing works
C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration
Teesalu, T., Sugahara, K. N., Kotamraju, V. R., & Ruoslahti, E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908201106 · Cited by 812 · see citing works
Self-citationDavidson, A. D., Williamson, M. K., Lewis, S., Shoemark, D., Carroll, M. W., Heesom, K. J., Zambon, M., Ellis, J., Lewis, P. A., Hiscox, J. A., et al. (2020) · Genome Medicine · doi:10.1186/s13073-020-00763-0 · Cited by 457 · see citing works
Self-citationPhysiological and molecular triggers for SARS-CoV membrane fusion and entry into host cells
Millet, J. K., & Whittaker, G. R. (2017) · Virology · doi:10.1016/j.virol.2017.12.015 · Cited by 291 · see citing works
Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction
Lau, S.-Y., Wang, P., Mok, B. W.-Y., Zhang, J., Chu, H., Lee, A. C.-Y., Deng, S., Chen, P., Chan, K., Song, W., et al. (2020) · Emerging Microbes & Infections · doi:10.1080/22221751.2020.1756700 · Cited by 291 · see citing works
Hollandi, R., Szkalisity, A., Toth, T., Tasnadi, E., Molnar, C., Mathe, B., Grexa, I., Molnar, J., Balind, A., Gorbe, M., et al. (2020) · Cell Systems · doi:10.1016/j.cels.2020.04.003 · Cited by 284 · see citing works
Self-citationBerger Rentsch, M., & Zimmer, G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025858 · Cited by 269 · see citing works
Structural basis for ligand and heparin binding to neuropilin B domains
Kooi, C. W. V., Jusino, M. A., Perman, B., Neau, D. B., Bellamy, H. D., & Leahy, D. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700043104 · Cited by 228 · see citing works
Appleton, B. A., Wu, P., Maloney, J. A., et al. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601906 · Cited by 218 · see citing works
Neuropilin Functions as an Essential Cell Surface Receptor
Guo, H., & Kooi, C. W. V. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.687327 · Cited by 202 · see citing works
Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex
Janssen, B. J. C., Malinauskas, T., Weir, G. A., Cader, M. Z., Siebold, C., & Jones, E. Y. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2416 · Cited by 197 · see citing works
An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability
Pang, H., Braun, G. B., Friman, T., Aza‐Blanc, P., Ruidíaz, M. E., Sugahara, K. N., Teesalu, T., & Ruoslahti, E. I. (2014) · Nature Communications · doi:10.1038/ncomms5904 · Cited by 196 · see citing works
Self-citationJarvis, A. N., Allerston, C., Jia, H., Herzog, B., Garza-Garcia, A., Winfield, N., Ellard, K., Aqil, R., Lynch, R., Chapman, C., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm901755g · Cited by 190 · see citing works
CIDRE: an illumination-correction method for optical microscopy
Smith, K., Li, Y., Piccinini, F., Csúcs, G., Balázs, C., Bevilacqua, A., & Horváth, P. (2015) · Nature Methods · doi:10.1038/nmeth.3323 · Cited by 188 · see citing works
Structural Basis for Selective Vascular Endothelial Growth Factor-A (VEGF-A) Binding to Neuropilin-1
Parker, M. W., Xu, P., Li, X., & Kooi, C. W. V. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.331140 · Cited by 186 · see citing works
Neuropilin Regulation of Angiogenesis, Arteriogenesis, and Vascular Permeability
Plein, A., Fantin, A., & Ruhrberg, C. (2014) · Microcirculation · doi:10.1111/micc.12124 · Cited by 125 · see citing works
Piccinini, F., Balassa, T., Szkalisity, Á., et al. (2017) · Cell Systems · doi:10.1016/j.cels.2017.05.012 · Cited by 89 · see citing works
Dorner, B. G., Steinbach, S., Hüser, M. B., Kroczek, R. A., & Scheffold, A. (2003) · Journal of Immunological Methods · doi:10.1016/s0022-1759(02)00498-2 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuroinvasion of SARS-CoV-2 in human and mouse brain
Song, E., Zhang, C., Israelow, B., Lu-Culligan, A., Prado, A. V., Skriabine, S., Lu, P., Weizman, O.-E., Liu, F., Dai, Y., et al. (2020) · doi:10.1101/2020.06.25.169946 · Cited by 1,064 · see citing works
N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
McCallum, M., De Marco, A., Lempp, F. A., Tortorici, M. A., Pinto, D., Walls, A. C., Beltramello, M., Chen, A., Liu, Z., Zatta, F., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.028 · Cited by 901 · see citing works
“, 2020), neuropilin-1 (Cantuti-Castelvetri et al., 2020; Daly et al., 2020) and L-SIGN/DC-SIGN (Chiodo et al.”
COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas
Ren, X., Wen, W., Fan, X., Hou, W., Su, B., Cai, P., Li, J., Liu, Y., Tang, F., Zhang, F., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.053 · Cited by 865 · see citing works
SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis
Wendisch, D., Dietrich, O., Mari, T., von Stillfried, S., Ibarra, I. L., Mittermaier, M., Mache, C., Chua, R. L., Knoll, R., Timm, S., et al. (2021) · Cell · doi:10.1016/j.cell.2021.11.033 · Cited by 528 · see citing works
SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis
Bayati, A., Kumar, R., Francis, V., & McPherson, P. S. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100306 · Cited by 499 · see citing works
Local and systemic responses to SARS-CoV-2 infection in children and adults
Yoshida, M., Worlock, K. B., Huang, N., Lindeboom, R. G. H., Butler, C. R., Kumasaka, N., Dominguez Conde, C., Mamanova, L., Bolt, L., Richardson, L., et al. (2022) · Nature · doi:10.1038/s41586-021-04345-x · Cited by 365 · see citing works
Morphological, cellular and molecular basis of brain infection in COVID-19 patients
Crunfli, F., Carregari, V. C., Veras, F. P., Vendramini, P. H., Valença, A. G. F., Antunes, A. S. L. M., Brandão-Teles, C., da Silva Zuccoli, G., Reis-de-Oliveira, G., Silva-Costa, L. C., et al. (2020) · doi:10.1101/2020.10.09.20207464 · Cited by 331 · see citing works
COVID-19 mRNA vaccines: Platforms and current developments
Szabó, G. T., Mahiny, A. J., & Vlatkovic, I. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.02.016 · Cited by 308 · see citing works
Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning
Drucker, D. J. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.01.016 · Cited by 272 · see citing works
Hoffmann, M., Hofmann-Winkler, H., Krüger, N., Kempf, A., Nehlmeier, I., Graichen, L., Arora, P., Sidarovich, A., Moldenhauer, A.-S., Winkler, M. S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109415 · Cited by 258 · see citing works
Tropism of SARS-CoV-2 for human cortical astrocytes
Andrews, M. G., Mukhtar, T., Eze, U. C., Simoneau, C. R., Ross, J., Parikshak, N., Wang, S., Zhou, L., Koontz, M., Velmeshev, D., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2122236119 · Cited by 159 · see citing works
Thacker, V. V., Sharma, K., Dhar, N., Mancini, G.-F., Sordet-Dessimoz, J., & McKinney, J. D. (2021) · The EMBO Reports · doi:10.15252/embr.202152744 · Cited by 142 · see citing works
Exosome-mediated mRNA delivery in vivo is safe and can be used to induce SARS-CoV-2 immunity
Tsai, S. J., Atai, N. A., Cacciottolo, M., Nice, J., Salehi, A., Guo, C., Sedgwick, A., Kanagavelu, S., & Gould, S. J. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101266 · Cited by 142 · see citing works
N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
McCallum, M., Marco, A. D., Lempp, F., Tortorici, M. A., Pinto, D., Walls, A. C., Beltramello, M., Chen, A., Liu, Z., Zatta, F., et al. (2021) · doi:10.1101/2021.01.14.426475 · Cited by 901 · see citing works
Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier?
Burks, S. M., Rosas-Hernandez, H., Alejandro Ramirez-Lee, M., Cuevas, E., & Talpos, J. C. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.12.031 · Cited by 97 · see citing works
Tackling COVID-19 with neutralizing monoclonal antibodies
Corti, D., Purcell, L. A., Snell, G., & Veesler, D. (2021) · Cell · doi:10.1016/j.cell.2021.07.027 · Cited by 78 · see citing works
“The RBD, and also the NTD, have been proposed to also interact with other receptors or co-receptors, including neuropilin-1 (NRP-1), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN or CD209), and liver-/lymph-node-specific intracellular adhesion molecules-3 grabbing non-integri…”
Pentón-Rol, G., Marín-Prida, J., & McCarty, M. F. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210408123807 · Cited by 73 · see citing works
Soh, W. T., Liu, Y., Nakayama, E. E., Ono, C., Torii, S., Nakagami, H., Matsuura, Y., Shioda, T., & Arase, H. (2020) · doi:10.1101/2020.11.05.369264 · Cited by 61 · see citing works
COVID-19 as a trigger for type 1 diabetes
Wang, Y., Guo, H., Wang, G., Zhai, J., & Du, B. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad165 · Cited by 50 · see citing works
Kruglova, N., Siniavin, A., Gushchin, V., & Mazurov, D. (2021) · Viruses · doi:10.3390/v13061133 · Cited by 37 · see citing works
Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids
Rahmani, W., Chung, H., Sinha, S., Bui-Marinos, M. P., Arora, R., Jaffer, A., Corcoran, J. A., Biernaskie, J., & Chun, J. (2022) · iScience · doi:10.1016/j.isci.2022.103818 · Cited by 25 · see citing works
Devaux, C. A., & Camoin-Jau, L. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1042200 · Cited by 20 · see citing works
Chen, H., Peng, J., Wang, T., Wen, J., Chen, S., Huang, Y., & Zhang, Y. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115370 · Cited by 19 · see citing works
- Authors
- Daly, J. L., Simonetti, B., Klein, K., Chen, K.-E., Williamson, M. K., Antón-Plágaro, C., Shoemark, D. K., Simón-Gracia, L., Bauer, M., Hollandi, R., Greber, U. F., Horvath, P., Sessions, R. B., Helenius, A., Hiscox, J. A., Teesalu, T., Matthews, D. A., Davidson, A. D., Collins, B. M., Cullen, P. J., & Yamauchi, Y.
- Affiliations
- University of Bristol (GB)
- The University of Queensland (AU)
- Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
- University of Zurich (CH)
- Synthetic and Systems Biology Unit, Biological Research Centre (BRC), Szeged, Hungary.
- ETH Zurich (CH)
- Agency for Science, Technology and Research (SG)
- University of Tartu (EE)
- Corresponding author
- Daly, James L.
- Simonetti, Boris
- Klein, Katja
- Chen, Kai-En
- Williamson, Maia Kavanagh
- Antón-Plágaro, Carlos
- Cullen, Peter J.
- Yamauchi, Yohei
- ORCID
- Venue
- Science
- Published
- 2020-11-13
- Volume
- 370
- Issue
- 6518
- Pages
- 861-865
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7612957
- OpenAlex
- W3094419073
- Cited by
- 1,251
- References
- 32
- Citations by year
- 2026: 28 · 2025: 79 · 2024: 111 · 2023: 173 · 2022: 312 · 2021: 461 · 2020: 85 · 2018: 1
- FWCI
- 33.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (acceptedVersion, other-oa)
- Funders
- U.S. Food and Drug Administration (HHSF223201510104C)
- H2020 European Research Council (No 856581 - CHUbVi)
- Medical Research Council (MR/P018807/1, MR/R020566/1)
- European Research Council (GLIOGUIDE)
- Swiss National Science Foundation
- Estonian Research Council (PRG230 and EAG79)
- European Regional Development Fund (2014-2020.4.01.15-0012)
- Wellcome Trust Centre for Mitochondrial Research (104568/Z/14/2)
- MRC-AMED (MR/T028769/1)
- LENDULET-BIOMAG (2018-342)
- H2020-discovAIR (874656)
- Wellcome Trust (203959/Z/16/Z)
- Beca Fundación Ramón Areces Estudios Postdoctorales en el Extranjero
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- neuropilin-1, SARS-CoV-2, host factors, viral entry, furin cleavage site, spike protein, viral tropism, antiviral agents, monoclonal antibodies, small molecule inhibitors, ACE2 receptor
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Antibodies, Monoclonal, HeLa Cells, Humans, Peptidyl-Dipeptidase A, Peptide Fragments, Pneumonia, Viral, Protein Binding, Mutagenesis, Site-Directed, Coronavirus Infections, Crystallography, X-Ray, Caco-2 Cells, Amino Acid Motifs, RNA Interference, Neuropilin-1, Furin, Virus Internalization, Protein Interaction Domains and Motifs, Pandemics, Spike Glycoprotein, Coronavirus
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
