Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Neuropilin-1 is a host factor for SARS-CoV-2 infection

James L. Daly, Boris Simonetti, Carlos Antón-Plágaro, Maia Kavanagh Williamson, Deborah K. Shoemark, Lorena Simón-Gracia, Katja Klein, Michael Bauer, Reka Hollandi, Urs F. Greber, Peter Horvath, Richard B. Sessions, Ari Helenius, Julian A. Hiscox, Tambet Teesalu, View ORCID ProfileDavid A. Matthews, Andrew D. Davidson, Peter J. Cullen, Yohei Yamauchi
doi: https://doi.org/10.1101/2020.06.05.134114
James L. Daly
1School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Boris Simonetti
1School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: pete.cullen@bristol.ac.uk
Carlos Antón-Plágaro
1School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maia Kavanagh Williamson
2School of Cellular and Molecular Medicine, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Deborah K. Shoemark
1School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lorena Simón-Gracia
3Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katja Klein
2School of Cellular and Molecular Medicine, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Bauer
4Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Reka Hollandi
5Synthetic and Systems Biology Unit, Biological Research Centre (BRC), Szeged, Hungary
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Urs F. Greber
4Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Horvath
5Synthetic and Systems Biology Unit, Biological Research Centre (BRC), Szeged, Hungary
6Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard B. Sessions
1School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ari Helenius
7Institute of Biochemistry, ETH Zurich, Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julian A. Hiscox
8Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tambet Teesalu
3Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David A. Matthews
2School of Cellular and Molecular Medicine, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David A. Matthews
Andrew D. Davidson
2School of Cellular and Molecular Medicine, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter J. Cullen
1School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: pete.cullen@bristol.ac.uk
Yohei Yamauchi
2School of Cellular and Molecular Medicine, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, BS8 1TD, U.K
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: pete.cullen@bristol.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

SARS-CoV-2 is the causative agent of COVID-19, a coronavirus disease that has infected more than 6.6 million people and caused over 390,000 deaths worldwide1,2. The Spike (S) protein of the virus forms projections on the virion surface responsible for host cell attachment and penetration. This viral glycoprotein is synthesized as a precursor in infected cells and, to be active, must be cleaved to two associated polypeptides: S1 and S2(3,4). For SARS-CoV-2 the cleavage is catalysed by furin, a host cell protease, which cleaves the S protein precursor at a specific sequence motif that generates a polybasic Arg-Arg-Ala-Arg (RRAR) C-terminal sequence on S1. This sequence motif conforms to the C-end rule (CendR), which means that the C-terminal sequence may allow the protein to associate with cell surface neuropilin-1 (NRP1) and neuropilin-2 (NRP2) receptors5. Here we demonstrate using immunoprecipitation, site-specific mutagenesis, structural modelling, and antibody blockade that, in addition to engaging the known receptor ACE2, S1 can bind to NRP1 through the canonical CendR mechanism. This interaction enhances infection by SARS-CoV-2 in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection, and provides a therapeutic target for COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted June 05, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Neuropilin-1 is a host factor for SARS-CoV-2 infection
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Neuropilin-1 is a host factor for SARS-CoV-2 infection
James L. Daly, Boris Simonetti, Carlos Antón-Plágaro, Maia Kavanagh Williamson, Deborah K. Shoemark, Lorena Simón-Gracia, Katja Klein, Michael Bauer, Reka Hollandi, Urs F. Greber, Peter Horvath, Richard B. Sessions, Ari Helenius, Julian A. Hiscox, Tambet Teesalu, David A. Matthews, Andrew D. Davidson, Peter J. Cullen, Yohei Yamauchi
bioRxiv 2020.06.05.134114; doi: https://doi.org/10.1101/2020.06.05.134114
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Neuropilin-1 is a host factor for SARS-CoV-2 infection
James L. Daly, Boris Simonetti, Carlos Antón-Plágaro, Maia Kavanagh Williamson, Deborah K. Shoemark, Lorena Simón-Gracia, Katja Klein, Michael Bauer, Reka Hollandi, Urs F. Greber, Peter Horvath, Richard B. Sessions, Ari Helenius, Julian A. Hiscox, Tambet Teesalu, David A. Matthews, Andrew D. Davidson, Peter J. Cullen, Yohei Yamauchi
bioRxiv 2020.06.05.134114; doi: https://doi.org/10.1101/2020.06.05.134114

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (2517)
  • Biochemistry (4964)
  • Bioengineering (3469)
  • Bioinformatics (15181)
  • Biophysics (6885)
  • Cancer Biology (5380)
  • Cell Biology (7711)
  • Clinical Trials (138)
  • Developmental Biology (4518)
  • Ecology (7135)
  • Epidemiology (2059)
  • Evolutionary Biology (10210)
  • Genetics (7497)
  • Genomics (9767)
  • Immunology (4822)
  • Microbiology (13179)
  • Molecular Biology (5129)
  • Neuroscience (29367)
  • Paleontology (203)
  • Pathology (835)
  • Pharmacology and Toxicology (1460)
  • Physiology (2129)
  • Plant Biology (4734)
  • Scientific Communication and Education (1008)
  • Synthetic Biology (1337)
  • Systems Biology (4002)
  • Zoology (768)