Variations within the glycan shield of SARS-CoV-2 impact viral spike dynamics
Variations within the glycan shield of SARS-CoV-2 impact viral spike dynamics
The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity, whether arisen naturally or through vaccination. Understanding the structure of the viral spike assists in determining the impact of mutations on the antigenic surface. One class of mutation impacts glycosylation attachment sites, which have the capacity to influence the antigenic structure beyond the immediate site of attachment. Here, we compare the site-specific glycosylation of recombinant viral spike mimetics of B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), B.1.1.529 (Omicron). The P.1 strain exhibits two additional N-linked glycan sites compared to the other variants analyzed and we investigate the impact of these glycans by molecular dynamics. The acquired N188 site is shown to exhibit very limited glycan maturation, consistent with limited enzyme accessibility. Structural modeling and molecular dynamics reveal that N188 is located within a cavity by the receptor binding domain, which influences the dynamics of these attachment domains. These observations suggest a mechanism whereby mutations affecting viral glycosylation sites have a structural impact across the protein surface.
glycosylation, mass spectrometry, molecular dynamics, SARS-CoV-2, variant of concern
Newby, Maddy L.
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Fogarty, Carl A.
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Allen, Joel D.
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Butler, John
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Fadda, Elisa
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Crispin, Max
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28 February 2023
Newby, Maddy L.
417cba47-6a6f-42b9-8b9c-640f0518c621
Fogarty, Carl A.
33e6619c-776e-4c6c-9161-bd0128e1d5ac
Allen, Joel D.
c873d886-2a66-475b-ae04-57a10b37e716
Butler, John
5132f0e2-f28d-412a-be9a-e97963b4c0ee
Fadda, Elisa
93020f1b-a98f-4f07-ab6c-4a1cc3810ba5
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Newby, Maddy L., Fogarty, Carl A., Allen, Joel D., Butler, John, Fadda, Elisa and Crispin, Max
(2023)
Variations within the glycan shield of SARS-CoV-2 impact viral spike dynamics.
Journal of Molecular Biology, 435 (4), [167928].
(doi:10.1016/j.jmb.2022.167928).
Abstract
The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity, whether arisen naturally or through vaccination. Understanding the structure of the viral spike assists in determining the impact of mutations on the antigenic surface. One class of mutation impacts glycosylation attachment sites, which have the capacity to influence the antigenic structure beyond the immediate site of attachment. Here, we compare the site-specific glycosylation of recombinant viral spike mimetics of B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), B.1.1.529 (Omicron). The P.1 strain exhibits two additional N-linked glycan sites compared to the other variants analyzed and we investigate the impact of these glycans by molecular dynamics. The acquired N188 site is shown to exhibit very limited glycan maturation, consistent with limited enzyme accessibility. Structural modeling and molecular dynamics reveal that N188 is located within a cavity by the receptor binding domain, which influences the dynamics of these attachment domains. These observations suggest a mechanism whereby mutations affecting viral glycosylation sites have a structural impact across the protein surface.
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Accepted/In Press date: 15 December 2022
e-pub ahead of print date: 21 December 2022
Published date: 28 February 2023
Additional Information:
Funding Information:
This work was supported by the International AIDS Vaccine Initiative (IAVI) through grant INV-008352/OPP1153692 funded by the Bill and Melinda Gates Foundation (M.C.). We also gratefully acknowledge support from the University of Southampton Coronavirus Response Fund (M.C.), and a donation from the Bright Future Trust (M.C.). The Science Foundation of Ireland (20/FFP-P/8809) is gratefully acknowledged for financial support (E.F.). The Irish Research Council is gratefully acknowledged for funding under the Government of Ireland Postgraduate Scholarship scheme (C.F.). The Irish Centre for High-End Computing (www.ichec.ie) is gratefully acknowledged for the generous allocation of computational resources (C.F. and E.F.). The opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the Science Foundation Ireland.
Publisher Copyright:
© 2022 The Author(s)
Keywords:
glycosylation, mass spectrometry, molecular dynamics, SARS-CoV-2, variant of concern
Identifiers
Local EPrints ID: 474406
URI: http://eprints.soton.ac.uk/id/eprint/474406
ISSN: 0022-2836
PURE UUID: 66b62608-234b-401c-90bb-7f62d5af1e16
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Date deposited: 21 Feb 2023 17:50
Last modified: 17 Mar 2024 03:47
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Contributors
Author:
Maddy L. Newby
Author:
Carl A. Fogarty
Author:
Joel D. Allen
Author:
Elisa Fadda
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