Michela Parafioriti
Evidence for multiple binding modes in the initial contact between SARS-CoV-2 spike S1 protein and cell surface glycans.
Parafioriti, Michela; Ni, Minghong; Petitou, Maurice; Mycroft‐West, Courtney J.; Rudd, Timothy R.; Gandhi, Neha S.; Ferro, Vito; Turnbull, Jeremy E.; Andrade De Lima, Marcelo A.; Skidmore, Mark A.; Fernig, David G.; Bisio, Antonella; Guerrini, Marco; Yates, Edwin A.; Elli, Stefano
Authors
Minghong Ni
Maurice Petitou
Courtney J. Mycroft‐West
Timothy R. Rudd
Neha S. Gandhi
Vito Ferro
Jeremy Turnbull j.e.turnbull@keele.ac.uk
Marcelo Andrade De Lima m.andrade.de.lima@keele.ac.uk
Mark Skidmore m.a.skidmore@keele.ac.uk
David G. Fernig
Antonella Bisio
Marco Guerrini
Edwin A. Yates
Stefano Elli
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.
Citation
Parafioriti, M., Ni, M., Petitou, M., Mycroft‐West, C. J., Rudd, T. R., Gandhi, N. S., …Elli, S. (2023). Evidence for multiple binding modes in the initial contact between SARS-CoV-2 spike S1 protein and cell surface glycans. Chemistry - A European Journal, 29(1), https://doi.org/10.1002/chem.202202599
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 22, 2022 |
Online Publication Date | Sep 22, 2022 |
Publication Date | Jan 2, 2023 |
Journal | Chemistry |
Print ISSN | 0947-6539 |
Publisher | Wiley |
Peer Reviewed | Peer Reviewed |
Volume | 29 |
Issue | 1 |
DOI | https://doi.org/10.1002/chem.202202599 |
Keywords | SARS-CoV-2; protein S spike; heparan sulfate; NMR spectroscopy; MD simulation |
Publisher URL | https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202202599 |
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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