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

Unfractionated heparin potently inhibits the binding of SARS-CoV-2 spike protein to a human cell line

Lynda J. Partridge, View ORCID ProfileLuke R. Green, Peter N. Monk
doi: https://doi.org/10.1101/2020.05.21.107870
Lynda J. Partridge
1Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luke R. Green
2Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Luke R. Green
  • For correspondence: l.r.green@sheffield.ac.uk
Peter N. Monk
2Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The SARS-CoV-2 spike protein is known to bind to the receptor, ACE2, on the surface of target cells. The spike protein is processed by membrane proteases, including TMPRSS2, and is either internalised or fuses directly with the cell, leading to infection. We identified a human cell line that expresses both ACE2 and TMPRSS2, the RT4 urinary bladder transitional carcinoma, and used it to develop a proxy assay for viral interactions with host cells. A tagged recombinant form of the spike protein, containing both the S1 and S2 domains, binds strongly to RT4 cells as determined by flow cytometry. Binding is temperature dependent and increases sharply at 37°C, suggesting that processing of the spike protein is likely to be important in the interaction. As the spike protein has previously been shown to bind heparin, a soluble glycosaminoglycan, we used a flow cytometry assay to determine the effect of heparin on spike protein binding to RT4 cells. Unfractionated heparin inhibited spike protein binding with an IC50 value of <0.05U/ml whereas two low molecular weight heparins were much less effective. This suggests that heparin, particularly unfractionated forms, could be considered to reduce clinical manifestations of COVID-19 by inhibiting continuing viral infection. Despite the sensitivity to heparin, we found no evidence that host cell glycosaminoglycans such as heparan and chondroitin sulphates play a major role in spike protein attachment.

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-ND 4.0 International license.
Back to top
PreviousNext
Posted May 21, 2020.
Download PDF

Supplementary Material

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.
Unfractionated heparin potently inhibits the binding of SARS-CoV-2 spike protein to a human cell line
(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
Unfractionated heparin potently inhibits the binding of SARS-CoV-2 spike protein to a human cell line
Lynda J. Partridge, Luke R. Green, Peter N. Monk
bioRxiv 2020.05.21.107870; doi: https://doi.org/10.1101/2020.05.21.107870
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Unfractionated heparin potently inhibits the binding of SARS-CoV-2 spike protein to a human cell line
Lynda J. Partridge, Luke R. Green, Peter N. Monk
bioRxiv 2020.05.21.107870; doi: https://doi.org/10.1101/2020.05.21.107870

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

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4372)
  • Biochemistry (9561)
  • Bioengineering (7075)
  • Bioinformatics (24800)
  • Biophysics (12581)
  • Cancer Biology (9929)
  • Cell Biology (14306)
  • Clinical Trials (138)
  • Developmental Biology (7935)
  • Ecology (12085)
  • Epidemiology (2067)
  • Evolutionary Biology (15965)
  • Genetics (10910)
  • Genomics (14716)
  • Immunology (9850)
  • Microbiology (23597)
  • Molecular Biology (9463)
  • Neuroscience (50750)
  • Paleontology (369)
  • Pathology (1537)
  • Pharmacology and Toxicology (2675)
  • Physiology (4003)
  • Plant Biology (8646)
  • Scientific Communication and Education (1506)
  • Synthetic Biology (2388)
  • Systems Biology (6417)
  • Zoology (1345)