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 ORCID: 0000-0003-4434-0333, Gandhi, Neha S, Ferro, Vito, Turnbull, Jeremy E ORCID: 0000-0002-1791-754X, Lima, Marcelo A, Skidmore, Mark A et al (show 5 more authors) (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). e202202599-.

Access the full-text of this item by clicking on the Open Access link.

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
Uncontrolled Keywords: SARS-CoV-2, protein S spike, heparan sulfate, NMR spectroscopy, MD simulation
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 13 Oct 2022 07:11
Last Modified: 04 Oct 2023 01:35
DOI: 10.1002/chem.202202599
Open Access URL: https://doi.org/10.1002/chem.202202599
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165162
Altmetric
Share
CORE (COnnecting REpositories)