NMR Experiments Provide Insights into Ligand-Binding to the SARS-CoV-2 Spike Protein Receptor-Binding Domain

Robert Creutznacher*, Thorben Maass, Barbora Veselkova, George Ssebyatika, Thomas Krey, Martin Empting, Norbert Tautz, Martin Frank, Knut Kölbel, Charlotte Uetrecht, Thomas Peters*

*Korrespondierende/r Autor/-in für diese Arbeit
1 Zitat (Scopus)


We have used chemical shift perturbation (CSP) and saturation transfer difference (STD) NMR experiments to identify and characterize the binding of selected ligands to the receptor-binding domain (RBD) of the spike glycoprotein (S-protein) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We also subjected full-length S-protein to STD NMR experiments, allowing correlations with RBD-based results. CSPs reveal the binding sites for heparin and fondaparinux, and affinities were measured using CSP titrations. We then show that α-2,3-sialyllactose binds to the S-protein but not to the RBD. Finally, combined CSP and STD NMR experiments show that lifitegrast, a compound used for the treatment of dry eye, binds to the linoleic acid (LA) binding pocket with a dissociation constant in the μM range. This is an interesting finding, as lifitegrast lends itself well as a blueprint for medicinal chemistry, eventually furnishing novel entry inhibitors targeting the highly conserved LA binding site.

ZeitschriftJournal of the American Chemical Society
Seiten (von - bis)13060-13065
PublikationsstatusVeröffentlicht - 27.07.2022

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)
  • Zentren: Zentrum für Medizinische Struktur- und Zellbiologie (ZMSZ)


  • 204-04 Virologie


  • Forschung zu SARS-CoV-2 / COVID-19