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

Sara Pollastri (1) , Clara Delaunay (2) , Michel Thépaut (2) , Franck Fieschi (2) , Anna Bernardi (1)

1 UNIMI - Università degli Studi di Milano = University of Milan
2 IBS - UMR 5075 - Institut de biologie structurale

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.

Domaines: Biologie structurale [q-bio.BM]

Sara Pollastri, Clara Delaunay, Michel Thépaut, Franck Fieschi, Anna Bernardi. Glycomimetic ligands block the interaction of SARS-CoV-2 spike protein with C-type lectin co-receptors. Chemical Communications, 2022, 58 (33), pp.5136-5139. ⟨10.1039/d2cc00121g⟩. ⟨hal-03714112⟩