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

Thorben Maass, George Ssebyatika, Marlene Brückner, Lea Breckwoldt, Thomas Krey, Alvaro Mallagaray, Thomas Peters*, Martin Frank, Robert Creutznacher

*Corresponding author for this work
1 Citation (Scopus)


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.

Original languageEnglish
Article numbere202202614
JournalChemistry - A European Journal
Issue number71
Publication statusPublished - 20.12.2022

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Structural and Cell Biology (CSCM/ZMSZ)

DFG Research Classification Scheme

  • 204-04 Virology
  • 204-05 Immunology

Coronavirus related work

  • Research on SARS-CoV-2 / COVID-19

Cite this