Recombinant SARS-CoV-2 S Protein Binds to Glycans of the Lactosamine Family in vitro

Abstract

Many viruses, beside binding to their main cell target, interact with other molecules that promote virus adhesion to the cell; often, these additional targets are glycans. The main receptor for SARS-CoV-2 is a peptide motif in the ACE2 protein. We studied interaction of the recombinant SARS-CoV-2 spike (S) protein with an array of glycoconjugates, including various sialylated, sulfated, and other glycans, and found that the S protein binds some (but not all) glycans of the lactosamine family. We suggest that parallel influenza infection will promote SARS-CoV-2 adhesion to the respiratory epithelial cells due to the unmasking of lactosamine chains by the influenza virus neuraminidase. Electronic supplementary material Supplementary material is available in the online version of this article at 10.1134/S0006297921030019 and on the journal website ( http://protein.bio.msu.ru/biokhimiya ).

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

“…Efforts to quantify these interactions on model sialylated species (for example, 3′-sialyllactose), however, were challenging and revealed weak binding (K d millimolar) 16 . Given this weak binding, it is not surprising that conflicting reports exist for the binding of the RBD to sialylated species by traditional glycan microarray screening 6,17,18 . Beyond acidic glycans, recent work suggests that the RBD mimics a galectin scaffold and can bind blood group A antigens 19 and terminal N-acetylglucosamine moieties (for example, GlcNAcα1-3GalNAcβ) 17 .…”

“…Given this weak binding, it is not surprising that conflicting reports exist for the binding of the RBD to sialylated species by traditional glycan microarray screening 6,17,18 . Beyond acidic glycans, recent work suggests that the RBD mimics a galectin scaffold and can bind blood group A antigens 19 and terminal N-acetylglucosamine moieties (for example, GlcNAcα1-3GalNAcβ) 17 . Moreover, it was recently reported that sialylated N-and O-glycans on ACE2 may play a role in S protein cell binding 20,21 .…”

Glycan Recognition in Human Norovirus Infections

“…There is less clear evidence of association of ABO blood groups with severe outcomes of the COVID-19 disease such as acute respiratory distress syndrome, kidney injury, intubation, intensive care unit (ICU) admission, or mortality. Two biochemical studies using glycan arrays and ELISAs demonstrate the binding of SARS-CoV-2 spike protein to A-type HBGAs [135,136]. The molecular basis of SARS-CoV-2 interactions with host HBGAs is unknown and the functional significance remains to be determined.…”

Viruses Like Sugars: How to Assess Glycan Involvement in Viral Attachment

“…The authors proposed a mechanism linked to the prevention of optimal interaction between ACE-2, which is sialylated, and the spike protein. However, an alternative explanation is suggested by a different publication [96]. The enhancement of infection after the removal of SA might be mediated by the exposure of lactosamine, which was the top hit of a 'reverse' glycan array performed by the authors.…”