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

Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

View ORCID ProfileSo Young Kim, Weihua Jin, Amika Sood, David W. Montgomery, Oliver C. Grant, Mark M. Fuster, Li Fu, Jonathan S. Dordick, Robert J. Woods, Fuming Zhang, Robert J. Linhardt
doi: https://doi.org/10.1101/2020.04.14.041459
So Young Kim
1Department of Medicine, Division of Pulmonary and Critical Care, University of California San Diego, La Jolla, California, United States of America
2VA San Diego Healthcare System, Medical and Research Sections, La Jolla, California, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for So Young Kim
  • For correspondence: y0k001@health.ucsd.edu zhangf2@rpi.edu linhar@rpi.edu
Weihua Jin
6Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amika Sood
4Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David W. Montgomery
5Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliver C. Grant
5Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark M. Fuster
1Department of Medicine, Division of Pulmonary and Critical Care, University of California San Diego, La Jolla, California, United States of America
2VA San Diego Healthcare System, Medical and Research Sections, La Jolla, California, United States of America
3Glycobiology Research and Training Center, University of California San Diego, La Jolla, California, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Fu
6Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan S. Dordick
7Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert J. Woods
5Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fuming Zhang
7Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: y0k001@health.ucsd.edu zhangf2@rpi.edu linhar@rpi.edu
Robert J. Linhardt
6Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York, United States of America
7Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States of America
8Department of Biological Science, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States of America
9Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: y0k001@health.ucsd.edu zhangf2@rpi.edu linhar@rpi.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 spike more tightly bind to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 μM, 0.12 μM, and 26.4 μM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Our study augments our knowledge in SARS-CoV-2 pathogenesis and advances carbohydrate-based COVID-19 therapeutic development.

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. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 15, 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.
Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry
(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
Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry
So Young Kim, Weihua Jin, Amika Sood, David W. Montgomery, Oliver C. Grant, Mark M. Fuster, Li Fu, Jonathan S. Dordick, Robert J. Woods, Fuming Zhang, Robert J. Linhardt
bioRxiv 2020.04.14.041459; doi: https://doi.org/10.1101/2020.04.14.041459
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry
So Young Kim, Weihua Jin, Amika Sood, David W. Montgomery, Oliver C. Grant, Mark M. Fuster, Li Fu, Jonathan S. Dordick, Robert J. Woods, Fuming Zhang, Robert J. Linhardt
bioRxiv 2020.04.14.041459; doi: https://doi.org/10.1101/2020.04.14.041459

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 (4666)
  • Biochemistry (10324)
  • Bioengineering (7649)
  • Bioinformatics (26274)
  • Biophysics (13490)
  • Cancer Biology (10659)
  • Cell Biology (15386)
  • Clinical Trials (138)
  • Developmental Biology (8474)
  • Ecology (12795)
  • Epidemiology (2067)
  • Evolutionary Biology (16812)
  • Genetics (11377)
  • Genomics (15443)
  • Immunology (10589)
  • Microbiology (25112)
  • Molecular Biology (10183)
  • Neuroscience (54296)
  • Paleontology (399)
  • Pathology (1663)
  • Pharmacology and Toxicology (2888)
  • Physiology (4330)
  • Plant Biology (9221)
  • Scientific Communication and Education (1585)
  • Synthetic Biology (2548)
  • Systems Biology (6766)
  • Zoology (1459)