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Binding of Glycans to the SARS CoV-2 Spike Protein,an Open Question: NMR Data on Binding Site Localization,Affinity, and Selectivity |
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| Authors: | Thorben Maass Dr George Ssebyatika Marlene Brückner Lea Breckwoldt Prof?Dr Thomas Krey Dr Alvaro Mallagaray Prof?Dr Thomas Peters Dr Martin Frank Dr Robert Creutznacher |
| Institution: | 1. Institute of Chemistry and Metabolomics, Center of Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany;2. Institute of Biochemistry, Center of Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany;3. Institute of Biochemistry, Center of Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
Centre for Structural Systems Biology (CSSB), Notkestraße 85, 22607 Hamburg, Germany German Center for Infection Research (DZIF) Partner Site Hamburg-Luebeck-Borstel-Riems, Ratzeburger Allee 160, 23562 Lübeck, Germany Cluster of Excellence RESIST (EXC 2155) and Institute of Virology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany;4. Biognos AB, 40274 Göteborg, Sweden;5. Institute of Chemistry and Metabolomics, Center of Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany Present address R.C.: Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, University of Utrecht, Yalelaan 1, 3584 CL Utrecht (The, Netherlands |
| Abstract: | We have used NMR experiments to explore the binding of selected glycans and glycomimetics to the SARS CoV-2 spike glycoprotein (S-protein) and to its receptor binding domain (RBD). STD NMR experiments confirm the binding of sialoglycans to the S-protein of the prototypic Wuhan strain virus and yield dissociation constants in the millimolar range. The absence of STD effects for sialoglycans in the presence of the Omicron/BA.1 S-protein reflects a loss of binding as a result of S-protein evolution. Likewise, no STD effects are observed for the deletion mutant Δ143–145 of the Wuhan S-protein, thus supporting localization of the binding site in the N-terminal domain (NTD). The glycomimetics Oseltamivir and Zanamivir bind weakly to the S-protein of both virus strains. Binding of blood group antigens to the Wuhan S-protein cannot be confirmed by STD NMR. Using 1H,15N TROSY HSQC-based chemical shift perturbation (CSP) experiments, we excluded binding of any of the ligands studied to the RBD of the Wuhan S-protein. Our results put reported data on glycan binding into perspective and shed new light on the potential role of glycan-binding to the S-protein. |
| Keywords: | blood group antigens carbohydrate-protein interactions sialoglycan spike glycoproteins STD NMR spectroscopy |