Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2.
Nat Chem Biol
; 18(1): 81-90, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1510604
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sialic Acids
/
Glycolipids
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
Limits:
Humans
Language:
English
Journal:
Nat Chem Biol
Journal subject:
Biology
/
Chemistry
Year:
2022
Document Type:
Article
Affiliation country:
S41589-021-00924-1
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