NMR Experiments Provide Insights into Ligand-Binding to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.
J Am Chem Soc
; 144(29): 13060-13065, 2022 07 27.
Article
en En
| MEDLINE
| ID: mdl-35830336
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Glicoproteína de la Espiga del Coronavirus
/
Tratamiento Farmacológico de COVID-19
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania