The SARS-CoV-2 Spike Glycoprotein Directly Binds Exogeneous Sialic Acids: A NMR View

Abstract

[EN] The interaction of the SARS CoV2 spike glycoprotein with two sialic acid-containing trisaccharides (alpha 2,3 and alpha 2,6 sialyl N-acetyllactosamine) has been demonstrated by NMR. The NMR-based distinction between the signals of those sialic acids in the glycans covalently attached to the spike protein and those belonging to the exogenous alpha 2,3 and alpha 2,6 sialyl N-acetyllactosamine ligands has been achieved by synthesizing uniformly C-13-labelled trisaccharides at the sialic acid and galactose moieties. STD-H-1,C-13-HSQC NMR experiments elegantly demonstrate the direct interaction of the sialic acid residues of both trisaccharides with additional participation of the galactose moieties, especially for the alpha 2,3-linked analogue. Additional experiments with the spike protein in the presence of a specific antibody for the N-terminal domain and with the isolated receptor binding and N-terminal domains of the spike protein unambiguously show that the sialic acid binding site is located at the N-terminal domain.