Glycomimetic ligands block the interaction of SARS-CoV-2 spike protein with C-type lectin co-receptors

Chem Commun (Camb). 2022 Apr 21;58(33):5136-5139. doi: 10.1039/d2cc00121g.

Abstract

The C-type lectin receptors DC-SIGN and L-SIGN bind to glycans on the SARS-CoV-2 spike glycoprotein and promote trans-infection of ACE2-expressing cells. We tested C2 triazole-modified mono- and pseudo-di-mannosides as inhibitors of DC/L-SIGN binding to a model mannosylated protein (Man-BSA) and to SARS-CoV2 spike, finding that they inhibit the interaction of both lectins with the spike glycoprotein in a Surface Plasmon Resonance (SPR) assay and are more potent than mannose by up to 36-fold (DC-SIGN) and 10-fold (L-SIGN). The molecules described here are the first known glycomimetic ligands of L-SIGN.

MeSH terms

  • COVID-19*
  • Humans
  • Lectins, C-Type / metabolism
  • Ligands
  • Protein Binding
  • RNA, Viral / metabolism
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus* / metabolism

Substances

  • Lectins, C-Type
  • Ligands
  • RNA, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2