*10.1. Glycosylation*

Glycosylation of viral proteins is a common theme among enveloped viruses due to their hydrophobic natures [251]. Glycosylation facilitates proper folding of the nascent polypeptide through recruitment of chaperone proteins and can play a role in cellular trafficking [251]. Cellular glycosylation also plays important roles in homeostasis and receptor

signaling [252], which can be hijacked by viruses [251]. Viruses may utilize glycosylation to mimic or complement host proteins for receptor binding and entry, viral assembly/release, and/or immune evasion [251]. Several CoV E proteins and all S proteins contain N-linked and O-linked glycosylation sites. N-linked glycosylation is characterized by covalent en block binding of an N-linked 14-unit glycan precursor [253] onto an asparagine residue located within a recognition sequence Asn-X-Ser/Thr [254], where X is any amino acid except proline [251]. Attachment of the N-linked glycan to the Asn-X-Ser/Thr is performed by the enzyme, oligosaccharyltransferase, followed by further modifications by glycosidases and glycosyltransferases [231]. O-linked glycosylation involves the attachment of an oligosaccharide to the side chain oxygen atom of a serine or threonine residue, initially through the activity of N-acetylgalactosamine (GalNAc) transferase, and this reaction does not require a consensus sequence as does N-linked glycosylation. Rather than occurring en block, simple sugar residues are sequentially added after the initial O-linked addition. N- and O-linked glycosylations can occur simultaneously and do not compete with each other.
