Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hoffmann, D; Mereiter, S; Jin, Oh, Y; Monteil, V; Elder, E; Zhu, R; Canena, D; Hain, L; Laurent, E; Grünwald-Gruber, C; Klausberger, M; Jonsson, G; Kellner, MJ; Novatchkova, M; Ticevic, M; Chabloz, A; Wirnsberger, G; Hagelkruys, A; Altmann, F; Mach, L; Stadlmann, J; Oostenbrink, C; Mirazimi, A; Hinterdorfer, P; Penninger, JM.
Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites.
EMBO J. 2021; 40(19): e108375
Doi: 10.15252/embj.2021108375
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- Co-Autor*innen der Med Uni Graz
- Jonsson Gustav
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- Abstract:
- New SARS-CoV-2 variants are continuously emerging with critical implications for therapies or vaccinations. The 22 N-glycan sites of Spike remain highly conserved among SARS-CoV-2 variants, opening an avenue for robust therapeutic intervention. Here we used a comprehensive library of mammalian carbohydrate-binding proteins (lectins) to probe critical sugar residues on the full-length trimeric Spike and the receptor binding domain (RBD) of SARS-CoV-2. Two lectins, Clec4g and CD209c, were identified to strongly bind to Spike. Clec4g and CD209c binding to Spike was dissected and visualized in real time and at single-molecule resolution using atomic force microscopy. 3D modelling showed that both lectins can bind to a glycan within the RBD-ACE2 interface and thus interferes with Spike binding to cell surfaces. Importantly, Clec4g and CD209c significantly reduced SARS-CoV-2 infections. These data report the first extensive map and 3D structural modelling of lectin-Spike interactions and uncovers candidate receptors involved in Spike binding and SARS-CoV-2 infections. The capacity of CLEC4G and mCD209c lectins to block SARS-CoV-2 viral entry holds promise for pan-variant therapeutic interventions.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Binding Sites - physiology
- COVID-19 - virology
- Cell Line - administration & dosage
- Chlorocebus aethiops - administration & dosage
- Glycosylation - administration & dosage
- HEK293 Cells - administration & dosage
- Humans - administration & dosage
- Mice - administration & dosage
- Molecular Dynamics Simulation - administration & dosage
- Protein Binding - physiology
- Receptors, Mitogen - metabolism
- SARS-CoV-2 - metabolism
- Vero Cells - administration & dosage
- Virus Internalization - administration & dosage
- Find related publications in this database (Keywords)
- glycosylation
- lectin
- SARS-CoV-2
- spike