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

Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain

View ORCID ProfileCourtney J. Mycroft-West, View ORCID ProfileDunhao Su, View ORCID ProfileYong Li, View ORCID ProfileScott E. Guimond, View ORCID ProfileTimothy R. Rudd, View ORCID ProfileStefano Elli, View ORCID ProfileGavin Miller, View ORCID ProfileQuentin M. Nunes, Patricia Procter, View ORCID ProfileAntonella Bisio, View ORCID ProfileNicholas R. Forsyth, View ORCID ProfileJeremy E. Turnbull, View ORCID ProfileMarco Guerrini, View ORCID ProfileDavid G. Fernig, View ORCID ProfileEdwin A. Yates, View ORCID ProfileMarcelo A. Lima, View ORCID ProfileMark A. Skidmore
doi: https://doi.org/10.1101/2020.04.29.068767
Courtney J. Mycroft-West
1Molecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, ST5 5BG, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Courtney J. Mycroft-West
Dunhao Su
2Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Dunhao Su
Yong Li
2Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yong Li
Scott E. Guimond
3School of Medicine, Keele University, Newcastle-Under-Lyme, Staffordshire, ST5 5BG, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Scott E. Guimond
Timothy R. Rudd
4National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, EN6 3QG, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timothy R. Rudd
Stefano Elli
5Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Via G. Colombo 81, 20133, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Stefano Elli
Gavin Miller
6School of Chemistry, Keele University, Newcastle-Under-Lyme, Staffordshire, ST5 5BG, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gavin Miller
Quentin M. Nunes
7Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3BX, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Quentin M. Nunes
Patricia Procter
1Molecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, ST5 5BG, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Antonella Bisio
5Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Via G. Colombo 81, 20133, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Antonella Bisio
Nicholas R. Forsyth
8Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Hartshill, Stoke-on-Trent, ST4 7QB
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicholas R. Forsyth
Jeremy E. Turnbull
2Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jeremy E. Turnbull
Marco Guerrini
5Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Via G. Colombo 81, 20133, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marco Guerrini
David G. Fernig
2Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David G. Fernig
Edwin A. Yates
2Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
1Molecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, ST5 5BG, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Edwin A. Yates
Marcelo A. Lima
1Molecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, ST5 5BG, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marcelo A. Lima
Mark A. Skidmore
1Molecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, ST5 5BG, UK
2Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mark A. Skidmore
  • For correspondence: m.a.skidmore@keele.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The glycosaminoglycan (GAG) class of polysaccharides are utilised by a plethora of microbial pathogens as receptors for adherence and invasion. The GAG heparin prevents infection by a range of viruses when added exogenously, including the S-associated coronavirus strain HSR1 and more recently we have demonstrated that heparin can block cellular invasion by SARS-CoV-2. Heparin has found widespread clinical use as anticoagulant drug and this molecule is routinely used as a proxy for the GAG, heparan sulphate (HS), a structural analogue located on the cell surface, which is a known receptor for viral invasion. Previous work has demonstrated that unfractionated heparin and low molecular weight heparins binds to the Spike (S1) protein receptor binding domain, inducing distinct conformational change and we have further explored the structural features of heparin with regard to these interactions. In this article, previous research is expanded to now include a broader range of GAG family members, including heparan sulphate. This research demonstrates that GAGs, other than those of heparin (or its derivatives), can also interact with the SARS-CoV-2 Spike S1 receptor binding domain and induce distinct conformational changes within this region. These findings pave the way for future research into next-generation, tailor-made, GAG-based antiviral agents, against SARS-CoV-2 and other members of the Coronaviridae.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Joint senior authors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 29, 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.
Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain
(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
Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain
Courtney J. Mycroft-West, Dunhao Su, Yong Li, Scott E. Guimond, Timothy R. Rudd, Stefano Elli, Gavin Miller, Quentin M. Nunes, Patricia Procter, Antonella Bisio, Nicholas R. Forsyth, Jeremy E. Turnbull, Marco Guerrini, David G. Fernig, Edwin A. Yates, Marcelo A. Lima, Mark A. Skidmore
bioRxiv 2020.04.29.068767; doi: https://doi.org/10.1101/2020.04.29.068767
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain
Courtney J. Mycroft-West, Dunhao Su, Yong Li, Scott E. Guimond, Timothy R. Rudd, Stefano Elli, Gavin Miller, Quentin M. Nunes, Patricia Procter, Antonella Bisio, Nicholas R. Forsyth, Jeremy E. Turnbull, Marco Guerrini, David G. Fernig, Edwin A. Yates, Marcelo A. Lima, Mark A. Skidmore
bioRxiv 2020.04.29.068767; doi: https://doi.org/10.1101/2020.04.29.068767

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

  • Biochemistry
Subject Areas
All Articles
  • Animal Behavior and Cognition (4397)
  • Biochemistry (9630)
  • Bioengineering (7123)
  • Bioinformatics (24939)
  • Biophysics (12670)
  • Cancer Biology (9995)
  • Cell Biology (14404)
  • Clinical Trials (138)
  • Developmental Biology (7989)
  • Ecology (12147)
  • Epidemiology (2067)
  • Evolutionary Biology (16025)
  • Genetics (10949)
  • Genomics (14778)
  • Immunology (9906)
  • Microbiology (23739)
  • Molecular Biology (9506)
  • Neuroscience (51050)
  • Paleontology (370)
  • Pathology (1545)
  • Pharmacology and Toxicology (2692)
  • Physiology (4038)
  • Plant Biology (8693)
  • Scientific Communication and Education (1512)
  • Synthetic Biology (2404)
  • Systems Biology (6458)
  • Zoology (1350)