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    Variations within the Glycan Shield of SARS-CoV-2 Impact Viral Spike Dynamics

    Newby, Maddy L. and Fogarty, Carl A. and Allen, Joel D. and Butler, John and 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). p. 167928. ISSN 0022-2836

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    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 molec- ular 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.

    Item Type: Article
    Keywords: SARS-CoV-2; glycosylation; variant of concern; mass spectrometry; molecular dynamics;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 16958
    Identification Number:
    Depositing User: Elisa Fadda
    Date Deposited: 21 Feb 2023 14:31
    Journal or Publication Title: Journal of Molecular Biology
    Publisher: Elsevier
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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