Parafioriti, M, Ni, M, Petitou, M, Mycroft-West, CJ, Rudd, TR, Gandhi, NS, Ferro, V, Turnbull, JE, Lima, MA, Skidmore, MA, Fernig, DG, Yates, EA, Bisio, A, Guerrini, M and Elli, S (2022) Evidence for multiple binding modes in the initial contact between SARS-CoV-2 spike S1 protein and cell surface glycans. Chemistry, 29 (1). ISSN 0947-6539

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Chemistry A European J - 2022 - Parafioriti - Evidence for multiple binding modes in the initial contact between SARS‐CoV‐2.pdf - Published Version
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Abstract

Infection of host cells by SARS-CoV-2 begins with recognition by the virus S (spike) protein of cell surface heparan sulfate (HS), tethering the virus to the extracellular matrix environment, and causing the subunit S1-RBD to undergo a conformational change into the 'open' conformation. These two events promote the binding of S1-RBD to the angiotensin converting enzyme 2 (ACE2) receptor, a preliminary step toward viral-cell membrane fusion. Combining ligand-based NMR spectroscopy with molecular dynamics, oligosaccharide analogues were used to explore the interactions between S1-RBD of SARS CoV-2 and HS, revealing several low-specificity binding modes and previously unidentified potential sites for the binding of extended HS polysaccharide chains. The evidence for multiple binding modes also suggest that highly specific inhibitors will not be optimal against protein S but, rather, diverse HS-based structures, characterized by high affinity and including multi-valent compounds, may be required.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Wiley at https://doi.org/10.1002/chem.20220259 Please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: SARS-CoV-2; protein S spike; heparan sulfate; NMR spectroscopy; MD simulation
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 31 Oct 2022 17:18
Last Modified: 21 Feb 2023 10:32
URI: https://eprints.keele.ac.uk/id/eprint/11647

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