**4. Therapeutic approach of glycomedicine**

Developments within the field of glycobiology have enabled the development of a range of glycan-based medical specialties. As an example, envelope conjugated protein gp120 is expressed on the surface of HIV-1, and its variable glycosylation facilitates viral escape from immune detection. Adding new glycan-dependent epitopes to the recombinant gp120 used for vaccination inflated the ability of broadly speaking neutralizing being antibodies to recognize HIV-1, suggesting that this approach is used to optimize vaccination protocols and antigens. Moreover, HIV-1 envelope glycoproteins not solely differentiate HIV-1 clad however can even be wont to estimate the efficacy of vaccine regimens on the premise of protein binding to a panel of gp120 glycan-dependent epitopes 240. As printed antecedently,

glycosylation plays an important role in regulating purposeful immune responses through complex receptor–glycan motif interactions. This site is currently being exploited in Ig therapies [20].

## **4.1 Role of lectins in COVID 19 and activation of complement pathway**

Lectins, are glycan-binding proteins (GBPs) that are present in plants and lots of alternative species, are known to act with various glycan molecules either attached or released to a peptide backbone. This distinctive property has been explored within the development of analytics for glycan determination. Many relevant platforms are according to which lectin-based microarray has incontestable a utility in capturing glycan profiles of therapeutic compound glycoprotein [21].

As antecedently mentioned, the S-protein of SARS-CoV-2 encompasses a crucial role in infectious agent adhesion by binding to hACE2. Therefore, the disruption of this interaction is taken into account as a gorgeous target for antiviral medical care. Some non-mammalian-derived lectins (from plants and bacteria) are pointed as various antiviral agents against swallowed viruses thanks to their ability to acknowledge the glycans present within the structural proteins and to impair the initial steps of the infectious agent pathological process. Given the recent emergence of SARS-CoV-2, solely the glycoprotein isolated from Indian bean [Flt3 receptor-interacting glycoprotein (FRIL)] has been according up to now as an antiviral against this virus. FRIL may be a glucose/mannose glycoprotein conjointly called DLL-I. This protein molecule utterly inhibited the cytopathic result of SARS-CoV-2 (strain hCoV-19/Taiwan/NTU04/2020) toward Vero cells at higher concentrations [17, 21].

According to a study, evaluation of the in vitro antiviral activity of thirty three plant lectins toward coronaviruses (SARS-CoV and feline infectious redness virus). Mannose-binding agglutinins showed the best anti-SARS-CoV effects. Among the studied lectins, the upper selective indexes (SIs) were found for those isolated from alliaceous plant (APA; SI > 222.2), black mulberry (Morniga M II; SI > 62.5), and helleborine (EHA; SI > 55.5). Nettle (UDA) and common tobacco agglutinins (NICTABA), each specific for GlcNAc, conjointly showed promising activity. NICTABA and FTO have conjointly shown restrictive activity against different swallowed viruses as well as respiratory disease A/B, breakbone fever virus kind a pair of (DENV-2), herpes simplex virus varieties one and a pair of (HSV-1 and HSV-2) and human immunological disorder viruses (HIV-1/2). Other plant lectins are shown to exhibit restrictive action toward different coronaviruses. Some mannosebinding lectins: concanavalin A (Con A), amaryllis hybrid antibody (HHA), *Galanthus nivalis* antibody (GNA or GNL) one in every of these studies highlighted the importance of glycosylation within the sensibility of 2 kinds of coronaviruses (mouse liver disease virus and feline infectious redness virus) (**Figure 2**) [17, 21].

Non-plant-derived agglutinins also are pointed as promising agents against coronaviruses, e.g. the mannose-binding-lectins cyanovirin-N (from *Cyanobacterium protoctiste)* ellipsosporum and griffithsin (GRFT) (from red marine alga *Griffithsia* sp.) However, solely GRFT has been evaluated against SARS-CoV and MERS-CoV. This protein molecule binds to multiple sites of SARS-CoV and MERS-Cov glycoproteins with high affinity and inhibits infectious agent entry. In addition, this glycoprotein conjointly reduced the mortality and therefore the severity of fatal pneumonic infection iatrogenic by SARS-CoV in mice. This result is related to the decrease of pro-inflammatory cytokines in infected respiratory organ tissue [17–19, 21].

The mitogenicity and pro-inflammatory properties of lectins raise many queries relating to their worth to treat clinical conditions with severe inflammatory

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

**Figure 2.** *Crystal structure of different mannose specific lectins (structures adapted from RCSB PDB).*

elements, as seen in COVID-19. The broad-spectrum activity of those agents and therefore the techniques utilized in their style ought to be thought of within the hunt for anti-infective compounds toward SARS-CoV-2. These compounds ought to enhance the response iatrogenic by the immunogen, whereas keeping the equilibrium between body substance and cellular immune responses. Noteworthy to say that even the right induction of Th1-biased response, which is very important for defense against infectious agents, still remains a limitation for a few adjuvants.

Lectins are well-known to push the proliferation of lymphocytes and modulate the discharge of effectors molecules (cytokines and gas oxide) by immune cells. For example, many lectins are potent inducers of IL-12 and IFN-γ production that are key cytokines in the establishment of the Th1 axis. Some lectins may also bind to toll-like receptors and/or increase their expression levels, which can conjointly modulate the discharge of pro-inflammatory cytokines and increase the receptor's ability to acknowledge the pathogens. In fact, the improvement of Th1-based response is very important for protecting immunity against viruses and different intracellular pathogens thanks to the activation of cytotoxic cells (natural killer cells and TCD8 lymphocytes) and production of neutralizing antibodies concerned in immunologic memory. During this sense, the immunomodulatory properties of lectins build them attractive candidates for vaccine adjuvant. Some studies involving glycoprotein as an adjuvant for respiratory disease vaccines need special mention [21].

Innate immunity plays an essential role against numerous pathogens, in that, physical barriers complement components, coagulation cascade, antigen-presenting cells, and immunoglobulins synergistically regulate opsonisation, inflammation, and phagocytosis. Although the innate system might not determine each antigen getting into the host, it will acknowledge numerous microorganisms mainly based on pathogen-associated molecular patterns (PAMPs) present on the cell surface. The notable examples of PAMPs are bacterial peptidoglycan, lipopolysaccharides, mannans, lipoteichoic acids, bacterial DNA, double-stranded ribonucleic acid, glucans, and infective agent surface macromolecule. Duly, the complement system could be a wing of an innate immune response having varied biological effects against a good vary of bacteria, fungal, and infective agent infections [22].

The complement cascade consists of soluble factors and cell surface receptors which will sensitize and counteract against both invading and self-antigens. The complement system bridges the innate and accommodative reaction through humoral immunity, and by modulating T- and B-cell functions. Complement pathways, which, once activated, lead to consecutive protein reactions, breakdown of complement components C3 and C5, and end in by-products formation (C3a and C5a). These anaphylatoxins elicit an excessiveness of physiochemical responses that successively activate phagocytic cells, and release cytokines, chemokines, reactive element species (ROS), adhesion molecules, and inflammation at the site of infection. Immunoglobulin and cytokines are essential parts of antiviral immunity. In fact, there are 3 main phases of complement activation - (1) foreign molecule recognition, (2) convertase enzyme formation which will cleave C3 and C5, and (3) fabrication of MAC for cell lysis. The alternative, classical, and mannose-binding lectin (MBL) pathways are activation cascades of assorted host-pathogen interaction conditions, joining at the juncture C3, from wherever the central complement cascade proceeds. Among the 3 pathways of complement activation, the MBL pathway is primary in infective agent infections to induce a pro-inflammatory response. Detail Investigations involving the complement system activation by the lectin pathway in COVID-19 and diseases are in need of the hour [22, 23].
