Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites

EMBO J. 2021 Oct 1;40(19):e108375. doi: 10.15252/embj.2021108375. Epub 2021 Aug 23.


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.

Keywords: SARS-CoV-2; glycosylation; lectin; spike.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / physiology
  • COVID-19 / virology
  • Cell Line
  • Chlorocebus aethiops
  • Glycosylation
  • HEK293 Cells
  • Humans
  • Mice
  • Molecular Dynamics Simulation
  • Protein Binding / physiology
  • Receptors, Mitogen / metabolism*
  • SARS-CoV-2 / metabolism*
  • Vero Cells
  • Virus Internalization


  • Receptors, Mitogen