作者
Linh Nguyen,Kelli A. McCord,Duong T Bui,Kim M. Bouwman,Elena N. Kitova,Mohamed Elaish,Dhanraj Kumawat,Gour Chand Daskhan,Ilhan Tomris,Ling Han,Pradeep Chopra,Tzu-Jing Yang,Steven Willows,Andrew Mason,Lara K. Mahal,Todd L. Lowary,Lori J. West,Shang-Te Danny Hsu,Tom C. Hobman,Stephen M. Tompkins,Geert-Jan Boons,Robert P. de Vries,Matthew S. Macauley,John S. Klassen
摘要
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. Mass spectrometric profiling of a glycan library reveals that sialylated glycans, especially sialic acid-containing gangliosides, interact with the RBD of the SARS-CoV-2 spike protein and are involved in ACE2-dependent viral infection.