**3. Different type of glycosylation in human**

#### **3.1 N-linked glycosylation**

The covalently N-linked glycans are superimposed co-translationally to native polypeptides within the endoplasmic reticulum (ER) as blocks of fourteen sugars (Glc3Man9GlcNAc2). These glycans are measure then subject to extensive modification throughout their transport through the ER and also the Golgi body before reaching their final destinations within or outside the cell. Within the ER and also the early secretory pathway, the sugar repertoire is still very little. Within the Golgi body, however, the glycans acquire complicated and extremely numerous structures by terminal glycosylation, which ends up in a very tremendous heterogeneity. Such diversity differs between cell sorts, tissues and species, and helps to additional increase microheterogeneity in the presence of the same genetic polypeptide background. This leads to the creation of new functionalities and specificities. The N-glycans may also have a very important role in correct macromolecule folding and degradation, and solubility, by avoiding the precipitation that's caused by lipophylic aminoacid stretches within the emergent polypeptide. The presence of a glycan protect on the peptides additionally allows the protection of the glycoproteins against degradation by proteases [13, 14].

#### **3.2 O-linked glycosylation**

Glycosylation will occur on amino acids with functional hydroxyl group teams, that is most frequently Ser and Thr. In humans, the foremost common sugars joined to Ser or Thr are GlcNAc and N-acetylgalactosamine (GalNAc)7. GalNAc-linked glycans usually referred to as mucin-type O-glycans, are abundant on various living things and secreted glycoproteins together with mucins, which type an important interface between animal tissue cells and the external tissue layer surfaces of the body. Mucins are characterized by a variable range of tandem repeats with Ser and Thr that create many sites for O-glycosylation. O-glycosylation performs various functions, such as providing resistance to proteolysis of stem regions of membrane proteins, creating specific recognition phenomena, and selection of ligands for selectins. Masking of immunogenic epitopes on the protein is in need to special mention [13, 14].

#### **3.3 Glycosphingolipids**

GSLs comprise a sphingolipid to which a glycan is connected at the C1 group position of a ceramide; they are one in every of the foremost plentiful glycolipids in humans are generally found within the lipid bilayers of cellular membranes. GSL glycosylation starts with the addition of glucose or galactose to the lipid moiety at the protoplasm facet of the ER or the Golgi body; however, the structure is then flipped to the luminal side for the additional process. The enzymes that initiate GSL glycosylation are specific for lipids, but an additional process of the sugar chain is performed by additional general glycosyltransferase [13, 14].

#### **3.4 Proteoglycans and glycosaminoglycans**

Proteoglycans are glycoproteins within the extracellular matrix that, in addition to containing canonical N-glycans and O-glycans, are characterized by the presence *Glycan and Its Role in Combating COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.97240*

of long sugar repeats connected via O-linked glycosylation motifs [13, 14]. These extended sugar chains are termed glycosaminoglycans and contribute to a considerable proportion of the proteoglycan's molecular mass. Whereas N-glycans generally embrace 5–12 monosaccharides, a glycosaminoglycan motif will simply contain more than eighty sugars (for example, keratan salt is a poly-N-acetyl lactosamine chain that contains up to fifty oligosaccharide units). These long chains are constructed through oligosaccharide repeats fashioned by GlcNAc or GalNAc, combined with associate uronic acid (that is, glucuronic or iduronic acid) or brain sugar. Glycosaminoglycans are functionally various and include heparan salt, chondroitin salt, keratin sulfate, and hyaluronan. Glycosaminoglycans are crucial to the formation of the glycocalyx, an important structure for the upkeep of the cytomembrane that conjointly functions as a reservoir for sequestered growth factors [13–15].

## **3.5 Role of glycans in immunity and inflammation**

Cells of the immune system, equally to any or all different cells, express cell surface-associated glycoproteins and glycolipids that, besides glycan-binding proteins and different molecules, sense environmental signals. Many immune receptors that are expressed on innate and adaptive immune cells acknowledge glycans found on the surface of microorganisms that are referred to as pathogen-associated molecular patterns. Examples of such glycan-containing molecules embrace bacterial lipopolysaccharides, peptidoglycans, teichoic acids, capsular polysaccharides, and fungal mannans. The recognition of those glycosylated microbial patterns by the immune system has been exploited for the vaccine's development, example diplococcus vaccines, are developed employing a mixture of capsular polysaccharides. The recent progress in HIV-1 immunogen development has conjointly been driven by a far better understanding of the HIV-1 envelope (Env) conjugated protein and the effects of its glycan composition on immune responses and immune evasion [15, 16].

Pro-inflammatory cytokines may contribute to inflammatory vascular diseases by inducing changes in cell-surface N-glycosylation of epithelial tissue cells. In the adaptive immune system, glycans even have crucial and multifarious roles in B lymphocyte and lymphocyte differentiation. These functions involve multiple cell-surface and secreted proteins (such as CD43, CD45, selectins, galectins, and siglecs), differing kinds of cell–cell interactions, and also the recognition of glycancontaining antigens. The regulation of cellular glycosylation and its impact on the molecules that perform as ligands and receptors throughout associate inflammatory response is controlled through numerous mechanisms and is dependent on the inflammatory insult. These mechanisms, that embrace ERK, and p65 signaling are vital to understanding the failure to regulate chronic inflammation in multiple disease states. Immunoglobulins, for instance, are crucial parts of humoral immunity, and altered glycosylation patterns of some antibody isotypes are known in chronic inflammatory reaction, and infectious diseases, like arthritis (RA), systemic lupus erythematosus (SLE), and HIV infection [16, 17].

The glycoproteins CD43 and CD45 are profusely expressed on the surface of B cells and T cells and contain each O-glycans and N-glycans. Glycosylation of those proteins is modulated throughout cellular differentiation and activation and regulates multiple T cell functions, as well as cellular migration, T cell receptor signaling, cell survival, and apoptosis. CD45 has an active receptor-like protein tyrosine phosphatase domain that interacts with Src family kinases in B cells and T cells to control the signaling threshold for the activation of B lymphocyte receptors (BCRs) and T cell receptors. CD45 additionally has non-catalytic functions, for instance, in modulating the function of the repressive co-receptor CD22 on B cells [17, 18].

Siglecs are sialic acid-binding proteins expressed on several cells of the system that perform varied functions, as well as the regulation of antigen-specific immune responses and cell homing. CD22 is one in all sixteen siglec proteins characterized in humans and is expressed on B cells, wherever it specifically binds α-2, 6-linked sialic acid-containing ligands; this interaction is crucial for the formation of nanoclusters within the cell wall that manage BCR signaling following antigen binding [17, 18].

The selectin family of proteins consists of E-selectin, P-selectin, and L-selectin that are chiefly expressed on epithelium cells, platelets, and leukocytes, respectively. These cell adhesion molecules are vital for white cells rolling on the epithelial tissue before tissue extravasations. Another study demonstrates that targeting selectins could be helpful in some inflammatory diseases. Immunoglobulin isotypes disagree within the variety of N-glycans present on their serious chains. Some immunoglobulin, such as IgA1 and immune globulin, additionally contain O-glycans, which are sometimes clustered within the hinge-region segments of these antibodies. Immunoglobulin glycans impact the effect or functions of antibodies counting on the branching of N-glycans and/or the terminal sugars of N-glycans or O-glycans that embody brain sugar and sialic acid. In fact, immunoglobulin glycosylation can verify glycoform is pro-inflammatory, like Ig with galactose-deficient N-glycans, or anti-inflammatory drug, like Ig with sialylated N-glycans [17–19].

#### **3.6 Glycan and COVID-19**

Coronavirus illness 2019 (Covid-19) has a broad clinical spectrum, not nevertheless absolutely delineate or understood, with a regarding the potential for severe respiratory illness, multiorgan involvement, and death. As a result of containment of the virus has verified to be very troublesome, mitigation efforts like mask-wearing, physical distancing, confinement, and quarantines are enforced worldwide leading to restricted exposures/contagious events with also a robust social, health, and economic burden [2]. Since ideal preventive ways like repurposing of known medication to treat Covid-19, and vaccines associated with inevitably long testing, development, and producing time emerges as an attractive approach to timely fulfill the continued need.

Glycoproteins of SARS-CoV-2 are concerned with cell adhesion and invasion, maturation, and modulation response processes. Though alternative SARS-CoV-2 proteins have foreseeable glycosylation sites (such as M-protein, E-protein), the bulk of experimental knowledge is presently accessible on the S-protein. This might be a trimeric protein that mediates viral adhesion through binding to the human angiotensin-converting accelerator two (hACE2) and conjointly interacts with the host immune defense [19, 20].

The S-protein from SARS-CoV-2 has 2 practical subunits (S1 and S2) with 23 potential sites for N-glycosylation and O-glycosylation. Some variations within the glycosylation sites repertoire and famed epitopes are rumored for the SARS-CoV-2 spike protein, despite it's similarity with the SARS-CoV spike (approximately 87.2%). The oligo mannose-type glycans were predominant in 2 sites (N234 and N709). Complex-type glycans were preponderantly exhibited in fourteen organic compound residues (N17, N74, N149, N165, N282, N331, N343, N616, N657, N1098, N1134, N1158, N1173, and N1194), whereas six sites showed a combination of oligomannose- and complex-type glycans (N1074, N801, N717, N603, N122, and N61). The foremost common configuration of oligomannose-type glycans was Man5GlcNAc2. Afucosylated and fucosylated hybrid-type glycans were detected in a minimum of 9 sites. Studies highlighted that the glycosylation profile of the

#### *Glycan and Its Role in Combating COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.97240*

SARS-CoV-2 S-protein was completely different from those discovered for host glycoproteins or for alternative engulfed viruses. Another experimental study revealed the configuration of the N-glycosylation and O-glycosylation of spike protein subunits, even in the HEK293-based expression system. The authors have solved the structures of N-linked glycans in seventeen foretold sites and rumored the presence of three categories of N-glycans. Significantly, this study discovered O-glycosylation modifications on 2 residues (Thr323 and Ser325) present within the receptor-binding domain (RBD) of the S1 monetary unit. Recently, the characterization of the glycosylation profile of the S-protein expressed in BTI-Tn-5B1–4 insect cells was rumored to show the presence of high-mannose N-glycans altogether twenty two foretold sites. Apparently, these glycans cowl most of the RBD space [17, 20].

The glycan shield plays a vital role in hiding the S protein surface from molecular recognition. However, to effectively operate, the spike has to recognize and bind to ACE2 receptors as the primary host cell infection route. For this reason, the RBM should become totally exposed and accessible. During this state of affairs, the glycan shield works in concert with an oversized conformational amendment that permits the RBD to emerge on top of the N-glycan coverage. The glycans protect the RBD region that does not directly act with ACE2 by "up" and "down" conformations. Ultimately, this analysis shows that the RBM is often accessible once RBD is "up", whereas it's terribly well camouflaged when "down". This implies that the glycan shield of this vital domain is effectively paired with its "down-to-up" conformational amendment, allowing the RBM to transiently emerge from the glycan shield and bind to ACE2 receptors [16, 19, 20].

Protein glycosylation plays a crucial role in the infective agent pathological process, as incontestable by the characteristically thick N-glycan coating of the infective agent fusion proteins. Within the HIV-1 envelope spike (Env), as an example, the protein-accessible expanse is nearly entirely coated in N-glycans. These are thus densely packed that they account for quite half the protein's mass. The N-glycans present on the surface of viral envelope glycoproteins show terribly diverse type of biological roles. Infective agent entry through membrane fusion is initiated by envelope glycoproteins through molecular recognition events involving cell surface receptors, which are usually mediated by specific N-glycan epitopes. Furthermore, an extremely dense coating of nonimmunogenic or frail immunogenic advanced carbohydrates on otherwise perilously exposed infective agent proteins constitutes a perfect camouflage (or shield) to evade the immune system. To the current study, the HIV-1 Env glycan defends, which is essentially structured by oligomannose (Man5–9) N-glycans, has been shown to be quite effective in allowing the virus to thwart the system [16, 17, 19].
