Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain

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Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain. / Schuurs, Zachariah P.; Hammond, Edward; Elli, Stefano; Rudd, Timothy R.; Mycroft-West, Courtney J.; Lima, Marcelo A.; Skidmore, Mark A.; Karlsson, Richard; Chen, Yen-Hsi; Bagdonaite, Ieva; Yang, Zhang; Ahmed, Yassir A.; Richard, Derek J.; Turnbull, Jeremy; Ferro, Vito; Coombe, Deirdre R.; Gandhi, Neha S.

In: Computational and Structural Biotechnology Journal, Vol. 19, 2021, p. 2806-2818.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schuurs, ZP, Hammond, E, Elli, S, Rudd, TR, Mycroft-West, CJ, Lima, MA, Skidmore, MA, Karlsson, R, Chen, Y-H, Bagdonaite, I, Yang, Z, Ahmed, YA, Richard, DJ, Turnbull, J, Ferro, V, Coombe, DR & Gandhi, NS 2021, 'Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain', Computational and Structural Biotechnology Journal, vol. 19, pp. 2806-2818. https://doi.org/10.1016/j.csbj.2021.05.002

APA

Schuurs, Z. P., Hammond, E., Elli, S., Rudd, T. R., Mycroft-West, C. J., Lima, M. A., Skidmore, M. A., Karlsson, R., Chen, Y-H., Bagdonaite, I., Yang, Z., Ahmed, Y. A., Richard, D. J., Turnbull, J., Ferro, V., Coombe, D. R., & Gandhi, N. S. (2021). Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain. Computational and Structural Biotechnology Journal, 19, 2806-2818. https://doi.org/10.1016/j.csbj.2021.05.002

Vancouver

Schuurs ZP, Hammond E, Elli S, Rudd TR, Mycroft-West CJ, Lima MA et al. Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain. Computational and Structural Biotechnology Journal. 2021;19:2806-2818. https://doi.org/10.1016/j.csbj.2021.05.002

Author

Schuurs, Zachariah P. ; Hammond, Edward ; Elli, Stefano ; Rudd, Timothy R. ; Mycroft-West, Courtney J. ; Lima, Marcelo A. ; Skidmore, Mark A. ; Karlsson, Richard ; Chen, Yen-Hsi ; Bagdonaite, Ieva ; Yang, Zhang ; Ahmed, Yassir A. ; Richard, Derek J. ; Turnbull, Jeremy ; Ferro, Vito ; Coombe, Deirdre R. ; Gandhi, Neha S. / Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain. In: Computational and Structural Biotechnology Journal. 2021 ; Vol. 19. pp. 2806-2818.

Bibtex

@article{921e2f213a2942cdaf8811b0db8b1853,
title = "Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain",
abstract = "SARS-CoV-2 has rapidly spread throughout the world's population since its initial discovery in 2019. The virus infects cells via a glycosylated spike protein located on its surface. The protein primarily binds to the angiotensin-converting enzyme-2 (ACE2) receptor, using glycosaminoglycans (GAGs) as co-receptors. Here, we performed bioinformatics and molecular dynamics simulations of the spike protein to investigate the existence of additional GAG binding sites on the receptor-binding domain (RBD), separate from previously reported heparin-binding sites. A putative GAG binding site in the N-terminal domain (NTD) of the protein was identified, encompassing residues 245-246. We hypothesized that GAGs of a sufficient length might bridge the gap between this site and the PRRARS furin cleavage site, including the mutation S247R. Docking studies using GlycoTorch Vina and subsequent MD simulations of the spike trimer in the presence of dodecasaccharides of the GAGs heparin and heparan sulfate supported this possibility. The heparan sulfate chain bridged the gap, binding the furin cleavage site and S247R. In contrast, the heparin chain bound the furin cleavage site and surrounding glycosylation structures, but not S247R. These findings identify a site in the spike protein that favors heparan sulfate binding that may be particularly pertinent for a better understanding of the recent UK and South African strains. This will also assist in future targeted therapy programs that could include repurposing clinical heparan sulfate mimetics. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.",
keywords = "Heparan sulfate, SARS-CoV-2, COVID-19, Spike protein, Heparin, Coronavirus, Cosolvent MD simulations, DELPHI WEB SERVER, HEPARAN-SULFATE, MOLECULAR-DYNAMICS, SOFTWARE NEWS, VISUALIZATION, ANTITHROMBIN, GROMACS, SYSTEM, GUI",
author = "Schuurs, {Zachariah P.} and Edward Hammond and Stefano Elli and Rudd, {Timothy R.} and Mycroft-West, {Courtney J.} and Lima, {Marcelo A.} and Skidmore, {Mark A.} and Richard Karlsson and Yen-Hsi Chen and Ieva Bagdonaite and Zhang Yang and Ahmed, {Yassir A.} and Richard, {Derek J.} and Jeremy Turnbull and Vito Ferro and Coombe, {Deirdre R.} and Gandhi, {Neha S.}",
year = "2021",
doi = "10.1016/j.csbj.2021.05.002",
language = "English",
volume = "19",
pages = "2806--2818",
journal = "Computational and Structural Biotechnology Journal",
issn = "2001-0370",
publisher = "Research Network of Computational and Structural Biotechnology (RNCSB)",

}

RIS

TY - JOUR

T1 - Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain

AU - Schuurs, Zachariah P.

AU - Hammond, Edward

AU - Elli, Stefano

AU - Rudd, Timothy R.

AU - Mycroft-West, Courtney J.

AU - Lima, Marcelo A.

AU - Skidmore, Mark A.

AU - Karlsson, Richard

AU - Chen, Yen-Hsi

AU - Bagdonaite, Ieva

AU - Yang, Zhang

AU - Ahmed, Yassir A.

AU - Richard, Derek J.

AU - Turnbull, Jeremy

AU - Ferro, Vito

AU - Coombe, Deirdre R.

AU - Gandhi, Neha S.

PY - 2021

Y1 - 2021

N2 - SARS-CoV-2 has rapidly spread throughout the world's population since its initial discovery in 2019. The virus infects cells via a glycosylated spike protein located on its surface. The protein primarily binds to the angiotensin-converting enzyme-2 (ACE2) receptor, using glycosaminoglycans (GAGs) as co-receptors. Here, we performed bioinformatics and molecular dynamics simulations of the spike protein to investigate the existence of additional GAG binding sites on the receptor-binding domain (RBD), separate from previously reported heparin-binding sites. A putative GAG binding site in the N-terminal domain (NTD) of the protein was identified, encompassing residues 245-246. We hypothesized that GAGs of a sufficient length might bridge the gap between this site and the PRRARS furin cleavage site, including the mutation S247R. Docking studies using GlycoTorch Vina and subsequent MD simulations of the spike trimer in the presence of dodecasaccharides of the GAGs heparin and heparan sulfate supported this possibility. The heparan sulfate chain bridged the gap, binding the furin cleavage site and S247R. In contrast, the heparin chain bound the furin cleavage site and surrounding glycosylation structures, but not S247R. These findings identify a site in the spike protein that favors heparan sulfate binding that may be particularly pertinent for a better understanding of the recent UK and South African strains. This will also assist in future targeted therapy programs that could include repurposing clinical heparan sulfate mimetics. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

AB - SARS-CoV-2 has rapidly spread throughout the world's population since its initial discovery in 2019. The virus infects cells via a glycosylated spike protein located on its surface. The protein primarily binds to the angiotensin-converting enzyme-2 (ACE2) receptor, using glycosaminoglycans (GAGs) as co-receptors. Here, we performed bioinformatics and molecular dynamics simulations of the spike protein to investigate the existence of additional GAG binding sites on the receptor-binding domain (RBD), separate from previously reported heparin-binding sites. A putative GAG binding site in the N-terminal domain (NTD) of the protein was identified, encompassing residues 245-246. We hypothesized that GAGs of a sufficient length might bridge the gap between this site and the PRRARS furin cleavage site, including the mutation S247R. Docking studies using GlycoTorch Vina and subsequent MD simulations of the spike trimer in the presence of dodecasaccharides of the GAGs heparin and heparan sulfate supported this possibility. The heparan sulfate chain bridged the gap, binding the furin cleavage site and S247R. In contrast, the heparin chain bound the furin cleavage site and surrounding glycosylation structures, but not S247R. These findings identify a site in the spike protein that favors heparan sulfate binding that may be particularly pertinent for a better understanding of the recent UK and South African strains. This will also assist in future targeted therapy programs that could include repurposing clinical heparan sulfate mimetics. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

KW - Heparan sulfate

KW - SARS-CoV-2

KW - COVID-19

KW - Spike protein

KW - Heparin

KW - Coronavirus

KW - Cosolvent MD simulations

KW - DELPHI WEB SERVER

KW - HEPARAN-SULFATE

KW - MOLECULAR-DYNAMICS

KW - SOFTWARE NEWS

KW - VISUALIZATION

KW - ANTITHROMBIN

KW - GROMACS

KW - SYSTEM

KW - GUI

U2 - 10.1016/j.csbj.2021.05.002

DO - 10.1016/j.csbj.2021.05.002

M3 - Journal article

C2 - 33968333

VL - 19

SP - 2806

EP - 2818

JO - Computational and Structural Biotechnology Journal

JF - Computational and Structural Biotechnology Journal

SN - 2001-0370

ER -

ID: 291018380