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SARS-CoV-2 Spike N-Terminal Domain Engages 9- O -Acetylated α2–8-Linked Sialic Acids by Ilhan Tomris; Luca Unione; Linh Nguyen; Pouya Zaree; Kim M. Bouwman; Lin Liu; Zeshi Li; Jelle A. Fok; María Ríos Carrasco; Roosmarijn van der Woude; Anne L. M. Kimpel; Mirte W. Linthorst; Sinan E. Kilavuzoglu; Enrico C. J. M. Verpalen; Tom G. Caniels; Rogier W. Sanders; Balthasar A. Heesters; Roland J. Pieters; Jesús Jiménez-Barbero; John S. Klassen; Geert-Jan Boons; Robert P. de Vries is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is SARS-CoV-2 Spike N-Terminal Domain Engages 9- O -Acetylated α2–8-Linked Sialic Acids about?

SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the spike protein contains a C-terminal receptor binding domain (RBD) and an N-terminal domain (NTD). The NTD of other coronaviruses includes a glycan binding cleft. However, for the SARS-CoV-2 NTD, protein–glycan binding was only observed weakly for sialic acids with highly sensitive methods. Amino acid changes in the NTD of variants of concern (VoC) show antigenic pressure, which can be an indication of NTD-mediated receptor binding. Trimeric NTD proteins of SARS-CoV-2, alpha, beta, delta, and omicron did not reveal a receptor binding capability. Unexpectedly, the SARS-CoV-2 beta subvariant strain (501Y.V2-1) NTD binding to Vero E6 cells was sensitive to sialidase pretreatment. Glycan microarray analyses identified a putative 9-__O__-acetylated sialic acid as a ligand, which was confirmed by catch-and-release ESI-MS, STD-NMR analyses, and a graphene-based electrochemical sensor. The beta (501Y.V2-1) variant attained an enhanced glycan binding modality in the NTD with specificity toward 9-__O__-acetylated structures, suggesting a dual-receptor functionality of the SARS-CoV-2 S1 domai

Who reads SARS-CoV-2 Spike N-Terminal Domain Engages 9- O -Acetylated α2–8-Linked Sialic Acids?

Author

Ilhan Tomris; Luca Unione; Linh Nguyen; Pouya Zaree; Kim M. Bouwman; Lin Liu; Zeshi Li; Jelle A. Fok; María Ríos Carrasco; Roosmarijn van der Woude; Anne L. M. Kimpel; Mirte W. Linthorst; Sinan E. Kilavuzoglu; Enrico C. J. M. Verpalen; Tom G. Caniels; Rogier W. Sanders; Balthasar A. Heesters; Roland J. Pieters; Jesús Jiménez-Barbero; John S. Klassen; Geert-Jan Boons; Robert P. de Vries

Publisher

American Chemical Society (ACS)

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)