20211109 Hsu STD Epub

Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2

Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2

Nat Chem Biol. 2022 Jan; 18(1):81-90. Epub 2021 Nov 9.
doi: 10.1038/s41589-021-00924-1


Nguyen L, McCord KA, Bui DT, Bouwman KM., Kitova EN, Elaish M, Kumawat D, Daskhan GC, Tomris I, Han L, Chopra P, Yang TJ, Willows SD, Mason AL, Mahal LK, Lowary TL, West LJ, Hsu STD, Hobman T, Tompkins SM, Boons GJ, de Vries RP, Macauley MS*, Klassen JS*


Emerging evidence suggests that host glycans influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal that the receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind to the RBD. The monomeric affinities (Kd = 100–200 μM) of gangliosides for the RBD are similar to another negatively charged glycan ligand of the RBD proposed as a viral co-receptor, heparan sulfate (HS) dp2–dp6 oligosaccharides. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to angiotensin-converting enzyme 2 (ACE2)-expressing cells is decreased following depletion of cell surface Sia levels using three approaches: sialyltransferase (ST) inhibition, genetic knockout of Sia biosynthesis, or neuraminidase treatment. These effects on RBD binding and both pseudotyped and authentic SARS-CoV-2 viral entry are recapitulated with pharmacological or genetic disruption of glycolipid biosynthesis. Together, these results suggest that sialylated glycans, specifically glycolipids, facilitate viral entry of SARS-CoV-2.