Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2
| Autor: | Shang-Te Danny Hsu, Gour Chand Daskhan, Linh Nguyen, Stephen M. Tompkins, Geert-Jan Boons, Elena N. Kitova, Todd L. Lowary, Tzu-Jing Yang, Ling Han, Kelli A. McCord, Mohamed Elaish, Duong T Bui, Robert P. de Vries, Ilhan Tomris, John S. Klassen, Kim M. Bouwman, Andrew Mason, Pradeep Chopra, Lori J. West, Lara K. Mahal, Steven Willows, Tom C. Hobman, Dhanraj Kumawat, Matthew S. Macauley |
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| Přispěvatelé: | Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery |
| Rok vydání: | 2021 |
| Předmět: |
Glycan
Binding Sites biology SARS-CoV-2 Chemistry Sialyltransferase viruses Cell Biology Heparan sulfate Ligand (biochemistry) Sialic acid carbohydrates (lipids) chemistry.chemical_compound Glycolipid Biochemistry Viral entry Spike Glycoprotein Coronavirus Sialic Acids biology.protein Humans Angiotensin-Converting Enzyme 2 Glycolipids Molecular Biology Neuraminidase |
| Zdroj: | Nature Chemical Biology, 18(1), 81. Nature Publishing Group |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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