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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
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 |
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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 |