# Important Roles of Oligo- and Polysaccharides
## 2 Oligo- and Polysaccharides against SARS-CoV-2
### Chitosan  
Chitosan is a naturally occurring cationic polysaccharide polymer with a high biodegradability, significant biocompatibility, and low toxicity, comprising \(\beta\)-(1-4) linkages of glucosamine units, which occurs rarely in nature, but is commonly generated from extensive \(N\)-deacetylation of chitin, a homopolymer of \(N\)-acetyl-glucosamine present in the exoskeletons of shrimp, shellfish and crabs, cutiles of insects, and cell walls of fungi [39, 40, 41]. This low-cost polysaccharide is environmentally benign, biodegradable, biocompatible, abundant, mucadhesive, and is a positively charged nontoxic biopolymer, which displays antiviral [42], antimicrobial [43], and immunoadjuvant effects, making it suitable for various medical and biomedical applications [44, 45, 41]. The amine groups (NH\({}_{2}\)) in chitosan-based materials are responsible for their various characteristics, including their cationic nature, in situ gelation, controlled drug release, antimicrobial, and mucoadhesion/permeation enhancement. Chitosan and its derivatives have been employed for cell encapsulation/delivery [46], 3D bioprinting [47], tissue engineering [48, 49], and delivery of biomolecule cargo (stimuli response release and targeted drug/gene delivery) [50, 51, 52]. Further, chitosan has been deployed for the encapsulation and coating of assorted nanoparticles (NPs), thereby fabricating diverse materials with appropriate potentials for the detection of diseases (e.g., cancers) [53, 54]. Additionally, it can be employed against pathogenic viruses, as has been reported in the case of curcumin chitosan nanocomposite (-29-39.5 nm) with their potential anti-hepatitis C virus effects, or the incitement of the inherent immune  
Figure 3: Some proposed mechanisms for antiviral performances of polysaccharides against SARS-CoV-2. EGFR: epidermal growth factor receptor; HSPG: heparan sulfate proteoglycan; RBD: receptor-binding domain. Reproduced with permission from Ref. [16]. system by the dispensation of chitosan via the nasal route for the protection of BALB/c mice from deadly contagion by the H7N9 virus (influenza A virus subtype H7N9) [55; 56]. Besides, chitosan NPs have been used as drug delivery systems/carriers for antiviral drugs, because of their good stability, low toxicity, and providing of versatile routes for their safe administration. As an example, these NPs were utilized for the delivery of didanosine (a medication typically used for the treatment of HIV/AIDS) for improvement of the systemic and brain targeting efficiency of this drug after intranasal administration [57]. SARS-CoV-2 via contact with human ACE2 can invade human respiratory epithelial cells [58]. In an impressive study, it has been illustrated that \(\beta\)-chitosan prevented the attachment, degradation, and internalization of ACE2 with SARS-CoV-2S-receptor-binding domain (RBD), and also inhibited the stimulation of inflammatory gesturing routes; \(\beta\)-chitosan's inhibitory effect on SARS-CoV-2S-RBD-triggered inflammation has been evaluated [58]. It was revealed that \(\beta\)-chitosan could effectively attach to SARS-CoV-2S-RBD or ACE2, and the ensuing conjugate of ACE2 and \(\beta\)-chitosan could not attach to SARS-CoV-2S-RBD anymore [58]. Remarkably, detection by immunofluorescence means on human ACE2 mice and Vero E6 cells showed that \(\beta\)-chitosan exhibited remarkable preventive and curative effects on SARS-CoV-2S-RBD attachment; this binding could stimulate the inflammation gesturing routes of mice and cells, but \(\beta\)-chitosan could noticeably subdue the SARS-CoV-2S-RBD-triggered inflammations. The conclusions from this study revealed that \(\beta\)-chitosan had an analogous antibody role, which can deactivate SARS-CoV-2S-RBD and can also be successfully applied for blocking the binding between SARS-CoV-2S-RBD and ACE2.