**1. Introduction**

A new virus called the 2019 novel coronavirus (an enveloped beta-coronavirus) is identified in December 2019 and associated with a de novo contagious respiratory disease. The coronavirus disease 2019 (COVID-19) has been declared as a "pandemic" by the World Health Organization (WHO). Previous reports have recognized various human coronaviruses, like in 2003 SARS-CoV, in 2004 HCoVNL63, in 2005 HKU1, in 2012 MERS-CoV, and now in 2019 pathogenic SARS-CoV-2. In humans, the effects of these viruses are correlated with severe respiratory tract infections. COVID-19 disease has signs that are similar to a common cold. However, this infection can lead to serious respiratory failure, as well as compromised and harmful immune responses. Increased monocyte-neutrophil ratios and exacerbated release of inflammatory mediators particularly IL-6, characterize this condition, which can contribute to organ dysfunction. Given the fact that other coronavirus outbreaks have occurred, there is no known treatment or vaccination for COVID-19.

Another major problem is the urgent need for easy and fast instruments to detect viruses in clinical and environmental samples. Early identification of SARS-CoV-2 in asymptomatic and/or presymptomatic individuals is crucial for stopping the transmission chain [1]. Plasmapheresis is also essential for extracorporeal removal of SARS-CoV-2 from blood in order to present alternative therapies. These dynamic pictures have imposed a fight against time through numerous fields of knowledge such as biomedical research, biotechnology, drug production, and molecular analysis in order to find as many resolutions as possible to these and other complications presented by the pandemic.

Viral members of the CoVs family restrain a positive-sense, single-strand RNA genome, which are 26 to 32- kilo bases in length [1]. The infectivity and immeasurable distribution capacity of CoVs have been established them as an important pathogen. In addition to numerous avian hosts, various members of CoVs have been recognized in a range of mammals, like masked palm civets, bats, dogs, mice, camels, and cats are responsible for disease related to gastrointestinal systems, hepatic, respiratory, and nervous system in humans. The outer surface membrane (M), envelope (E), and spike (S) structural proteins are coupled within the envelope of coronavirus which consists of a lipid bilayer. It is believed that glycosylated SARS-CoV-2 spike (S) protein, mediates host cell entry by binding to the angiotensin- converting enzyme 2 (ACE2) and establish the host tropism. Similar to many other viral fusion proteins, the SARS-CoV-2 spikes also utilize a highly dense coating of non-immunogenic or weakly immunogenic complex carbohydrates - glycan shield to thwart the host immune response [2]. Glycans are carbohydrate-based polymers made by all living organisms. The heavily glycosylated SARS-CoV spike protein suppresses almost 23 putative *N*-glycosylation sites, amidst 12 of them are effectively glycosylated [3]. In viral fusion proteins presence of N-glycan coating is correlated with protein glycosylation and plays a decisive role in viral pathogenesis. The N-glycans expressed on the surface of viral envelope glycoproteins have very diverse biological roles and are all inextricably linked to their nature. However, molecular recognition in between cell surface receptors and envelope glycoproteins are mediated by specific N-glycan epitopes and attribute to viral entry through membrane fusion. Moreover, an extremely dense coating of non-immunogenic or feeble immunogenic complicated carbohydrates on otherwise perilously exposed viral proteins constitutes an ideal camouflage (or shield) to evade the system [4].

The glycan shield plays a crucial role in concealing the surface S protein from molecular recognition. However, to effectively perform, the spike has to acknowledge and bind to ACE2 receptors as the primary infection route. For this reason, the RBM should become absolutely exposed and accessible. During this situation, the glycan shield works as one with an outsized conformational modification that permits the RBD to emerge higher than the N-glycan coverage. Each the S-glycoprotein and ACE2 receptor are proverbial to be extensively glycosylated, i.e. they contain covalently linked complex oligosaccharides referred to as glycans. Recently published studies have shown that the spike glycoprotein contains sixty-six glycosylation sites with forty-four of them being enclosed within the model. Another recent study analyzed site-specific N-linked glycosylation of MERS and respiratory illness SARS S glycoproteins, indicating that every of those glycosylation sites is occupied by up to 10 totally different glycans (called glycoforms), which greatly extends epitope diversity [4, 5].

The synthesis, folding, and glycosylation (as alternative PTMs) of infectious agent proteins depend upon host organelles (ribosome, endoplasmic reticulum, and Golgi apparatus) and enzymes (glycosyltransferases and glycosidases). The present experimental knowledge relating to the glycosylation of viral proteins depends on the carbohydrate processing enzymes present within the

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

biological systems accustomed to propagate the viral strain. During this sense, our data regarding the natural pattern of viral protein glycosylation is incredibly restricted. It's conjointly vital to think that viral proteins could follow totally different pathways than those discovered from host glycoproteins [5, 6]. Attribute to their chemical complexity and restricted sensitivity of existing analytical instruments, glycans are left neglected. This can be unfortunate as they verify a major part of the structure and performance of the many glycoproteins. This can be very true within the field of host/pathogen interactions, wherever glycan diversity is employed by each host to evade recognition by pathogens and therefore the pathogens to flee the system response. Moreover, glycans, and specifically their outmost components, have vital conformational flexibility. This contributes to the overall conformational dynamics of the molecule that may each generate novel potential drug binding sites or shield binding sites predicted mainly from polypeptide-only models [7].

Beyond a function in shielding the underlying proteins from recognition by antibodies, the glycans on infective proteins may additionally attenuate the flexibility of the host system to lift antibodies against any epitopes that embrace the glycan. In an exceedingly T-cell-dependent adaptative immune reaction, peptides from the infective agent are presented on antigen- presenting cells by major histocompatibility complex II molecules, conjointly referred to as human leukocyte antigen (HLA) complexes. HLA complexes have the most popular peptide antigen motifs, and supported data of those preferences it's doable to predict that peptides in exceedingly infective proteins are probably to be HLA antigens [8]. However, once that peptide contains a glycosylation site, the probability of the peptide to be presented in an HLA complex could also be compromised, if as an example the peptide cannot bind to the HLA molecule owing to the steric presence of the glycan. However, glycopeptides could also be presented in HLA complexes if the glycan is compact enough or if it's found on the end of the peptide antigen wherever it does not interfere with HLA binding. The glycan-mediated shielding of predicted HLA antigens derived from the S glycoprotein is conjointly containing a glycosite. Glycosylation systematically decreases the surface exposure of the residues proximal to the glycosites however conjointly junction rectifier to non-sequential changes in exposure, as a result of the 3D topology of the protein surface within the close proximity of every glycosite [8, 9].

The SARS-CoV-2 envelope glycoproteins are involved in the viral adhesion and entry processes. The presence of glycoproteins in the viral envelope opens up a world of possibilities for using carbohydrate-binding agents like lectins to fix some of the pandemic's most pressing issues. Lectins can recognize glycans, allowing them to be used in a number of biotechnological applications. The presence of glycoproteins on the viral envelope unfolds a large vary of prospects for the application of lectins to deal with some urgent issues concerned during this pandemic. The growing popularity of glycans enables the use of lectins for many biotechnological applications. Significantly, these agglutinins block the viral adhesion to the host cells by targeting the sugar moieties in surface proteins, and are considered as broad-spectrum inhibitors of viral invasion. The interaction with glycoproteins conjointly allows the use of lectins within the development of devices for identification and characterization of glycoproteins in a viral envelope or alterations in host glycoproteins throughout virus infection. Lectins are natural proteins that focus on the sugar moieties of a large vary of glycoproteins [10]. They are prevailing among higher plants and are divided into seven families of structurally and evolutionarily connected proteins. Over a decade ago, studies revealed that through inhibition of virus-cell fusion, plant lectins were reportable to inhibit HIV replication in lymphocyte cell cultures [9].

Sugar-binding proteins that are neither antibodies nor enzymes are known as lectins. To be labeled as a lectin, a glycoprotein must meet three distinct criteria. To begin, lectin is a carbohydrate-binding protein or glycoprotein (s). Second, lectins aren't the same as immunoglobulins (antibodies). Finally, lectins do not alter the biochemistry of the carbohydrates they bind. Plant lectins are a specific type of carbohydrate-binding proteins which are capable of specific recognition and reversible binding to carbohydrates. Since lectins can recognize specific carbohydrate structures such as proteoglycans, glycoproteins, and glycolipids, they can control various cells through glycoconjugates and their physiological and pathological phenomena via host-pathogen interactions and cell–cell communications.

Initially, it had been reported that plant lectins inhibit virus replication by forestalling virus adsorption however studies had been later shown that they prevent the fusion of HIV particles with their target cells. Additionally to the antiviral impact of mannose- and N-acetylglucosamine-specific agglutinins on HIV, the associate repressive impact of those plant lectins was reported on respiratory syncytial viral infection, CMV infection, and influenza A virus infection in vitro. Carbohydrate-binding agents are thought of as anti-CoV agents that focus on spike protein and restrain CoV entry [10]. They're proficient to bind specifically with the oligosaccharides on virus surfaces like HIV and S glycoprotein. In mouse model and additionally, in vitro condition they inhibit a large variety of CoVs, as well as SARS-CoV, HCoV NL63, HCoV 229E, and HCoV OC43. Plant lectins, such as those present in leeks, have been shown to be effective coronavirus inhibitors by interacting with two targets in the viral replication cycle. The first target was discovered early in the replication cycle, most likely during viral attachment, while the second was discovered toward the end of the infectious virus cycle. Depending on the nature of their sugar specificity, the antiviral activity spectrum of plant lectins varies considerably. In general, the plant lectins which were mannose-specific found to be highly effective against coronaviruses. Mannose-binding glycoprotein (MBL; additionally called mannan-binding lectin) could be a pattern-recognition molecule that plays a critical role in spacing and orientation of the carbohydrate-recognition domains [2, 10].

In several expression systems, glycosylation act as a live to gauge antigen quality. For styling appropriate immunogens for vaccine development, it is important to have basic understanding concomitant with the RBD domain of the SARS-CoV-2 spike protein which is able to incorporate complicated sialylated N-glycans and

#### **Figure 1.**

*Potential role of MBL in prevention of SARS-CoV2. 1. Attachment of MBL at the glycosylation site of spike protein by "Lock and Key" mode. 2. Prevent ACE2 mediated entry of viral pathogen. 3. Lectin pathwaymediated phagocytosis of intracellular pathogens (adapted from reference [2]).*

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

sialylated glycoprotein O-glycans. The interaction with glycoproteins additionally permits the utilization of lectins within the development of devices for the identification and characterization of glycoproteins in infectious agent envelopes or alterations in host glycoproteins throughout virus infection. MBL could be a serum C-type glycoprotein, that is in a position to bind SARS-CoV intrinsically or infected cell and additionally capable to inhibit the infectivity of the virus. Hence, with this background knowledge, we could to anticipate that glycosylation of infectious agent peptides by "Lock and Key Technology" may be considerate as a novel therapeutic strategy against the current COVID-19 pandemic (**Figure 1**) [2, 10, 11].

## **2. Glycosylation and its role in onset of disease**

The "glycome biology" or "glycobiology" studies the thorough repertoire i.e. the structure, biosynthesis, and biology of glycoconjugates composed of carbohydrate chains, or glycans, which are covalently, linked to lipid or protein molecules. The formation of glycoconjugates, differences in their glycan sequences, their length, and the connection between them depends upon on a process called glycosylation. Synthesis of glycoconjugate is a dynamic process that relies on the sugar precursors, the local milieu of enzymes, structures of organelle as well as cellular signals, and the cell types. Studies of rare genetic disorders that have an effect on glycosylation 1st highlighted the biological importance of the glycome, and technological advances have improved our understanding of its heterogeneousness and quality. However the replication process of secreted and cell-surface glycomes, overall cellular standing in health and sickness requires a detail research and assessment. In fact, changes in glycosylation will modulate inflammatory responses, alter viral immune escape, promote neoplastic cell metastasis, or regulate apoptosis; the composition of the glycome conjointly affects urinary organ operate in health and sickness. Easy and extremely dynamic protein-bound glycans also are well endowed within the nucleus and living substance of cells, wherever they exert restrictive effects. In fact, additionally to forming vital structural options, the sugar elements of glycoconjugates modulate or mediate a good form of functions in physiological and pathophysiological states. Glycoproteins and polysaccharides have vital functions in viral cells, and even glycoproteins have central roles within the biology of most viruses [10, 12]. Glycoconjugates are measured by the addition of sugars to proteins and lipids. A huge range of naturally occurring sugars will be combined to make a variety of distinctive glycan structures on lipid and protein molecules that modulate their activity. Multiple enzymatic site preferences, similarly because the use of stereochemical α or β conjugations, produce diversity in wherever and the way these sugars are linked to every alternative. In fact, altogether, these options imply the potential existence of ~1012 completely different branched glycan structures.

Protein glycosylation includes the addition of N-linked glycans, O-linked glycans, phosphorylated glycans, glycosaminoglycans, and glycosylphosphatidylinositol (GPI) anchors to amide backbones similarly to C-mannosylation of essential amino acid residues. Glycolipids are glycoconjugate which include glycosphingolipids (GSLs) formed through the addition of sugars to lipids. Glycosylation of proteins and lipids happens within the endoplasmic reticulum (ER) and with most of the terminal processing occurring within the cis-, medial- and trans-Golgi compartments. In these organelles, glycosidases, and glycosyltransferases form carbohydrate structures in a series of steps that are dominance by the availability of the enzyme activity, substrate, levels of gene transcription, and enzyme location. In fact, the glycome of a specific cell reflects its distinctive gene-expression pattern that controls the level of the enzymes responsible for glycoconjugation.

The glycome is created in a non-templated manner and is in an elaborate way controlled at multiple levels within the ER and cyst, unlike exome or proteome [12, 13].
