Table 1.

Summary of potential coreceptor ligands of the SARS-CoV-2 spike protein.

Ligand	Description	Proposed Virological Function	References
Sialic acid	Sugar chain with nine-carbon backbone found on the surfaces of all vertebrate cells. Implicated in various functions and diseases.	S1-NTD may bind sialic acids in a sialosides-binding pocket that resembles that of the MERS-CoV S1-NTD. Sialic acid may act as a coreceptor to help S1 reach ACE2 via viral surfing, or it may inhibit ACE2-S1 binding.	[4,11,17,46]
Monosialylated gangliosides (GM1, GM2, GM3)	Sialic acid-containing glycosphingolipids widely expressed in the nervous system. As part of the plasma membrane’s outer leaflet, these sugar chains are key to cell-cell recognition, adhesion, and signal transduction.	Negatively charged flat surface may attract the electropositive tip of virus envelope proteins. Association with cholesterol to form lipid rafts could enhance fusion. Membrane chaperone properties could enhance activation of viral proteins.	[19,21,47]
Heparan sulfate proteoglycans (HSPGs)	Glycoprotein with attached heparan sulfate polysaccharide chains. Found as a cellular receptor in almost all mammalian cells with functions related to development, inflammation, coagulation, angiogenesis, and viral entry.	Binding between HSPGs/HS and a polyanionic path along the S1-RBD, NTD, and FCS may enhance the open conformation of the RBD, supporting RBD-ACE2 binding.	[23,24,25,26]
Leucine-rich repeat-containing protein 15 (LRRC15)	Protein family with unrelated functions and characteristic α/β-horseshoe shape with leucine-rich tandem repeats. Functions of LRRC15 include innate immunity, down regulation of protein localization to the plasma membrane, and nervous system development.	LRRC15 may sequester and immobilize SARS-CoV-2 virions. Upregulated by proinflammatory cytokines, LRRC15 could suppress lung fibrosis during virus-induced inflammation. Demonstrated affinity for S1-NTD.	[31,32,33,34,35,37]
Neuropilin-1 (NRP-1)	Glycoprotein receptor found on cell membranes of neurons with functions related to angiogenesis, neuronal development, and immune response regulation.	Potentially enables SARS-CoV-2 virions to enter the nervous system through respiratory and olfactory epithelia. Known to bind furin-cleaved substrates.	[38,39,40]