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*

*Corresponding author for this work
1 Citation (Scopus)

Abstract

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.

Original languageEnglish
JournalJournal of the American Chemical Society
Volume144
Issue number29
Pages (from-to)13060-13065
Number of pages6
ISSN0002-7863
DOIs
Publication statusPublished - 27.07.2022

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

Coronavirus related work

  • Research on SARS-CoV-2 / COVID-19

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