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33 INNOSC Theranostics and Pharmacological Sciences, 2022, Vol. 5, No. 2 Das et al.
natural biopolymer with repeated chains of N-acetyl fibers in dressing materials. As a mucoadhesive
glucosamine and glucosamine. It possesses physical biopolymer, chitosan nanoparticles effectively
and biological functionality, is biodegradable, and encapsulate both hydrophilic and lipophilic
demonstrates biocompatibility with various organs, chemotherapeutic drugs, significantly improving
tissues, and cells, obviated with cytotoxic and the pharmacokinetic profile of the drug by increasing
noxious effects [4-6]. The efficiency of chitosan in its solubility and stability in the biological system.
biomedical applications, such as drug and vaccine Research has shown that hydroxypropyl trimethyl
delivery, antimicrobial properties (bactericidal, ammonium chloride chitosan (HTCC), a chitosan
virucidal, fungicidal, and anti-parasitic effects), polymer, interacts with the coronaviral spike (S)
wound healing, chitosan-guided bone regeneration, protein, effectively blocking its interaction with
and the preparation of artificial skin, hydrogel, and cellular receptors, thereby preventing the entry of
bio lenses for eyes have revolutionized polymer the virus into susceptible cells. This interaction
science [5,7-11]. Chitosan’s intermolecular and highlights the potential of HTCC as a potent broad-
intramolecular hydrogen bonds contribute to its spectrum antiviral drug, effectively hampering the
high crystallinity, making it almost insoluble in replication of severe acute respiratory syndrome
water and therefore limiting its applications to some coronavirus 2 (SARS-Cov-2) and MERS CoV in
extent. However, its adhesion capacity is amplified VeroE6/human aerial epithelium (HAE)/Huh-7 cell
by the presence of several reactive groups, making cultures, suggesting HTCC’s inhibitory activity
it an excellent natural biopolymer. Moreover, against the viral spike protein and its entry receptor
chitosan’s hydrophobicity and pH sensitivity enable interaction [17-19]. However, the exact mechanism
heterogeneous biomedical applications. By reacting of action for these quaternary ammonium chitosan
with various organic acids and their derivatives, remains unclear and their antiviral mode of action
chitosan can have aliphatic or aromatic acyl groups against other viruses has yet to be elucidated [18].
added to its chain [4,5]. Carboxylated chitosan, The S protein of the virus interacts with the
for instance, possesses higher water solubility and host cell membrane receptor called angiotensin-
exhibits better thickening, heat preservation, film converting enzyme 2 (ACE2), a monomeric
formation, flocculation, and kneading properties membrane-associated receptor on human cells,
than chitosan alone. The hydrophilic positively enabling SARS-CoV-2 to enter host cells. According
charged quaternary ammonium group plays a to Jena et al., 2021 [2], the receptor binding domain
crucial role in its properties. The higher degree of (RBD) of the S-glycoprotein of SARS-CoV-2
substitution (DS) in carboxyl chitosan improves binds ACE2. This RBD region is identical to that of
water solubility, increases its charge and strength, SARS-CoV. Targeting the RBD region of the spike
and weakens hydrogen bonding. Carboxymethyl protein could potentially impede viral attachment
chitosan, an active compound in the biomedical to the ACE2 receptor and prevent viral entry into
and pharmaceutical fields, exhibits antibacterial host cells, making it a promising target for viral
properties that promote wound healing. In addition, infection prevention [17]. While recent research has
it demonstrates lipid-lowering, anti-arteriosclerosis, proposed various natural products for developing or
antiviral, anti-tumor, anti-coagulation, and repurposing anti-SARS-CoV2 drugs that target the
hypoglycemic effects [12,13]. spike glycoprotein, to the best of our knowledge,
In recent years, the most commonly used none have explored the potential of chitosan and its
quaternary ammonium salts are 2,3-epoxypropyl derivatives for this purpose [18,19].
trimethyl ammonium chloride and 3-chloro-2- In a recently published research [16-18],
hydroxypropyl trimethyl ammonium chloride and several chitosan derivatives, namely, N-
N, N, N- trimethyl ammonium chloride [6,14-16]. octadecanoyl-N-3-carboxy propionyl chitosan,
Quaternary ammonium chitosan salt has demonstrated palmitoyl-trimethyl-chitosan, N-carboxymethyl
superior antibacterial, antiviral, biocompatible, chitosan (NCMC), N,O-carboxymethyl chitosan,
biodegradable, non-toxic, mucoadhesive, and anti- and carboxy ethyl chitosan, demonstrated
inflammatory properties, rendering them ideal filler effective actions against viral S protein and its

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