Among the number of specific adsorbents for human norovirus reported until now, histo-blood group antigens (HBGAs) are the most studied adsorbent. HBGAs are complex carbohydrates present in the outer part of N- or O- linked glycans of glycoproteins and glycolipids [
30]. ABH and Lewis HBGA families are present, and the secretor or non-secretor status is determined by the presence of fucosyltransferase2 (FUT2) [
31]. The biosynthesis of HBGAs occurs by sequential addition of monosaccharides to the type-1 or type-2 disaccharide precursors mediated by FUT2 (α-1,2 fucosyltransferase), FUT3 (α-1,3 or α-1,4 fucosyltransferase), and A and B transferases [
31,
32,
33]. HBGAs can be found on the surfaces of red blood cell and mucosal epithelial cells or are available as free oligosaccharides in bodily fluids like milk, saliva, and blood of secretor-positive (Se+) individuals [
31,
34]. Different norovirus strains have different HBGA-recognition profiles; up to now, eight distinct binding patterns have been recognized [
35,
36,
37]. The P2 subdomain of the norovirus capsid is directly responsible for receptor recognition [
38]. A study was conducted to determine the precise locations and binding modes of HBGAs on the viral capsids using a recombinant P protein of GII.4 VA387 strain cocrystallized with synthetic A or B trisaccharides [
38]. The results revealed that both A and B saccharides strongly interact with P protein of VA387 [
39]. α-fucose plays a central role in norovirus–receptor interactions, while β-galactose may not be crucial [
39]. The cavity which binds with α-fucose is formed by the β5 strand and residues S441, G442, and Y443 in one monomer and S343, T344, R345, and D374 in the other monomer [
37,
39]. The interface between P protein and fucose is dominated by hydrogen bonds. A recent study reported that not only the presence of a binding epitope but also the orientation of the receptor is critical for norovirus binding [
40]. Norovirus GII.4 strains that have evolved towards pandemic strains show increased relative affinity for HBGAs, and some of the recent variants have a broader host spectrum, including Lewis-positive non-secretors [
41,
42].
In addition to HBGAs, human norovirus has shown to attach to heparan sulphate [
43], sialylated glycans [
44], virus binding proteins recovered from activated sludge [
45,
46], and norovirus attachment proteins in mammalian cells [
47]. A study by Gandhi et al. [
48] reported specific binding of GI to the surface of romaine lettuce, cilantro, and iceberg lettuce via non-HBGA receptors which are not characterized yet. Almand et al. [
49] observed the binding of noroviruses GI.6, GII.4 New Orleans, GII.4 Sydney, and Tulane virus to a selected group of bacteria representing the human gut microbiome and found that all bacterial strains interacted with the virus strains. HBGAs were suspected to be the specific receptor, even though the specific receptors responsible for norovirus binding are yet to be identified. Several substances, such as human milk oligosaccharides [
50], glycerol [
51], and tannic acids [
52], are reported to inhibit the interaction between HBGA-like substances and human norovirus. Extensive reviews on the receptors interacting with human norovirus are available elsewhere [
53,
54].
Human norovirus surrogates are also shown to establish specific interactions with various receptors. Murine norovirus (MNV) can bind to GD1a located in the terminal sialic acids on murine macrophages and was confirmed to have a region topologically similar to the HBGA-binding site of norovirus VA387 strain [
55,
56]. Studies have confirmed the necessity of CD300lf for the binding and replication of MNV in cell lines [
57,
58]. Tulane virus binds to A-type 3 and B-type HBGAs and also recognizes sialic acids for cell attachment [
59,
60].