SARS-CoV-2 Spike N-Terminal Domain Engages 9- O -Acetylated α2-8-Linked Sialic Acids.

Autor: Tomris I; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Unione L; CICbioGUNE, Basque Research & Technology Alliance (BRTA), Bizkaia Technology Park, Building 800, 48160 Derio, Bizkaia, Spain.; Ikerbasque, Basque Foundation for Science, Maria Diaz de Haro 3, 48013 Bilbao, Bizkaia, Spain., Nguyen L; Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton T6G 2G2, Canada., Zaree P; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Bouwman KM; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Liu L; Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, United States., Li Z; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Fok JA; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Ríos Carrasco M; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., van der Woude R; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Kimpel ALM; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Linthorst MW; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Kilavuzoglu SE; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Verpalen ECJM; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Caniels TG; Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, 1081 HZ Amsterdam, The Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, 1081 HZ Amsterdam, The Netherlands., Sanders RW; Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, 1081 HZ Amsterdam, The Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, 1081 HZ Amsterdam, The Netherlands.; Department of Microbiology and Immunology, Weill Medical Center of Cornell University, 1300 York Avenue, New York, New York 10065, United States., Heesters BA; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Pieters RJ; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Jiménez-Barbero J; CICbioGUNE, Basque Research & Technology Alliance (BRTA), Bizkaia Technology Park, Building 800, 48160 Derio, Bizkaia, Spain.; Department of Microbiology and Immunology, Weill Medical Center of Cornell University, 1300 York Avenue, New York, New York 10065, United States.; Department of Organic Chemistry, II Faculty of Science and Technology University of the Basque Country, EHU-UPV, 48940 Leioa, Spain.; Centro de Investigación Biomédica En Red de Enfermedades Respiratorias, Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, 28029 Madrid, Spain., Klassen JS; Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton T6G 2G2, Canada., Boons GJ; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.; Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, United States., de Vries RP; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: ACS chemical biology [ACS Chem Biol] 2023 May 19; Vol. 18 (5), pp. 1180-1191. Date of Electronic Publication: 2023 Apr 27.
DOI: 10.1021/acschembio.3c00066
Abstrakt: 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 domain, which was quickly selected against. These results indicate that SARS-CoV-2 can probe additional evolutionary space, allowing binding to glycan receptors on the surface of target cells.
Databáze: MEDLINE
Externí odkaz: