Binding of Glycans to the SARS CoV-2 Spike Protein, an Open Question: NMR Data on Binding Site Localization, Affinity, and Selectivity

Chemistry. 2022 Sep 26. doi: 10.1002/chem.202202614. Online ahead of print.ABSTRACTWe have used NMR experiments to explore 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 binding of sialoglycans to the S-protein of the prototypic Wuhan strain virus and yield dissociation constants in the mM 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 Δ 143-145 of the Wuhan S-protein, 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 1 H, 15 N TROSY HSQC based chemical shift perturbation (CSP) experiments we exclude 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.PMID:36161798 | DOI:10.1002/chem.202202614
Source: Chemistry - Category: Chemistry Authors: Source Type: research