# Important Roles of Oligo- and Polysaccharides
## 2 Oligo- and Polysaccharides against SARS-CoV-2
### Heparin or Heparin-Like Materials  
Heparin, an assorted collection of anionic linear-chain mucopolysaccharides, is a component of a glycosaminoglycan family of molecules that comprise hyaluronic acid, keratan sulfate, chondroite sulfate, and heparan sulfate [60]. The main sugars, among others, present in heparin include \(\beta\)-D-glucuronic acid, \(\alpha\)-\(L\)-iduronic acid, \(\alpha\)-\(L\)-iduronic acid 2-sulfate, 2-deoxy-2-sulfamino-\(\alpha\)-D-glucose-6-sulfate, and 2-acetamido-2-deoxy-\(\alpha\)-D-glucose. Glycosaminoglycan entities are articulated all over the body, with different biological functions, and they are typically related to extracellular matrices (ECM), respiratory and endothelial cell surfaces, and basement membranes. Indeed, various pathogenic bacteria and viruses rest on communications with proteoglycans, namely heparan sulfate articulated on an array of human tissue exteriors, for the sticking to and incursion of host tissues. It was revealed that heparin competed with heparan sulfate for the bonding to bacteria and viruses, thus preventing or restricting the pathogenic invasions [60]. Recently, the antiviral effect of heparin and enoxaparin derivatives, including enoxaparin (IC\({}_{50}\) = 1.08 mg L\({}^{-1}\)), unfractionated heparin (IC\({}_{50}\) = 5.99 \(\mu\)g L\({}^{-1}\)), 6-O-desulfated unfractionated heparin (IC\({}_{50}\) = 1.77 \(\mu\)g L\({}^{-1}\)), and 6-O-desulfated enoxaparin (IC\({}_{50}\) = 5.86 mg L\({}^{-1}\)) has been reported against SARS-CoV-2; it was revealed that the binding of the SARS-CoV-2 spike glycoprotein to glycosaminoglycans (such as heparan sulfate) could be the reason for these inhibitory effects [61]. The viral invasion is typically related to the virus endocytosis, the virus's fusion with the cell membrane, and its translocation [9]. Heparin or its mimic substances endowed with wide-spread spectrum antiviral characteristics were utilized to imitate the cell surface carbohydrates accountable for the first viral bonding, such as carrageenanan and heparan sulfate [9]. Innovatively, the glycosaminoglycan-binding motif was inserted at the S1/S2 proteolytic cleavage site and additional such motifs within the SARS-CoV-2 spike glycoprotein, and it was proposed that glycosaminoglycans present on the cell surfaces of the host might liaise with SARS-CoV-2 spike glycoproteins to accelerate entry into the host cell [62]. It was uncovered that both the trimeric and monomeric SARS-CoV-2 spike glycoproteins could attach more firmly to the immobilized heparin than the MERS-CoV and SARS-CoV spike glycoproteins could. In one study, by adding heparin to Vero cells in the range of 6.25-200 \(\mu\)g mL\({}^{-1}\), the incursion by SARS-CoV-2 was inhibited to the extent of 44 and 80%; heparin could bind to the binding domain of the Spike (S1) protein receptor and promote a conformational modification [63]. Additionally, Au NPs, with no detectable cytotoxicity, either in a sulfonated form or coated with heparin, had wide-spectrum antiviral effects versus some pathogenic viruses (RSV, HPV, HSV, lentiivirus, and DENV), in vitro [64]. Therefore, future investigations may focus on the anti-CoVs activity of these nontoxic antiviral nanosystems with appropriate virucidal inhibitory efficacy. Brown seaweeds-originated sulfated polysaccharides have a structural similarity with glycosaminoglycans [5]. Assorted glycosaminoglycans, heparan sulfates, and heparin, along with additional sulfated polysaccharides and ticoidan, have been evaluated to analyze their affinity to attach to the SARS-CoV-2 S-protein. Intricate sulfated polysaccharides (fucoidans) acquired from the seaweed _Saccharina japonica_, RPI-27 and RPI-28, non-fractionated USP-heparin by itself, and chemo- enzymatically produced trisulfated heparin (TriS) were capable of competition with heparin to bind to the S-protein. Additionally, RPI-28 and RPI-27 did not show toxicity at the highest concentration in Vero cells via usual water-soluble tetrazolium salt-1 (WST-1) assay [5].