Glycomimetic ligands block the interaction of SARS-CoV-2 spike protein with C-type lectin co-receptors. Issue 33 (5th April 2022)

• Record Type: Journal Article
• Authors: Pollastri, Sara; Delaunay, Clara; Thépaut, Michel; Fieschi, Franck; Bernardi, Anna
• Is Part Of: Chemical communications. Volume 58:Issue 33(2022)
• Page Start: 5136
• Page End: 5139
• Publication Date: 2022-04-05
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d2cc00121g
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : DC-SIGN and its analogue L-SIGN work as co-receptors in many viral infections, including by SARS-CoV-2. Here we describe the first group of small-molecule glycomimetics that bind to L-SIGN, as well as to DC-SIGN, with micromolar affinity. 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.