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42 INNOSC Theranostics and Pharmacological Sciences, 2022, Vol. 5, No. 2 Das et al.
These findings suggest that HTCC has a strong align with the research conducted by Milewska
immuno-enhancing effect [32]. et al. in 2016 and 2021 [17,18].
The current alarming situation necessitates urgent In addition to mHTCC, carboxylated chitosan
research to proactively address the pathogenesis of derivatives have demonstrated efficient inhibitory
SARS-CoV-2 and prevent future outbreaks. The activity against the S protein, yielding binding
viral entry site is composed of the RBD domain energies of −7.9, −7.2, and −5.9 kcal/mol for
of the S protein (ranges from Arg 319 to Phe591) NCMC, N-carboxy ethyl chitosan, and N,O-
and the N-terminal peptidase domain of ACE2 carboxymethyl chitosan, respectively. These values
receptor (ranges from Ser19 to Asp615). When were ascertained through interactions with the S
ligands mHTCC bind with RBD, they interact with protein. NCMC exhibited a promising docking
Ser438, Asp442, Phe342, Ala344, Asn440, Asn343, score with both the RBD of the S protein and the
Asn437, Thr345, Trp436, Leu441, and Leu441, ACE2 receptor. This promising result paves the
which fall within the range of amino acids 319–591 way for further investigations, positioning it as
of the RBD domain. This region is well-known for a prospective candidate for robust biopolymer
its role in binding to host cells. Similarly, mHTCC development against SARS-CoV-2. Our study’s
binds with ACE2 receptor involving Lys562, observations reveal the enhanced binding affinity
Tyr196, Gln102, and Ala99, which are part of the of the carboxylated derivatives of chitosan
virus entry site (Figure 2). Moreover, NMNC binds subunits toward the S protein. Molecular docking
at the RBD site, interacting with Asn343, Arg509, studies reveal the efficacy of HTCC, NCMC,
Thr345, Ala344, Leu441, Trp436, Asp442, Ser438, N,O-carboxymethyl chitosan, and N-carboxy
Ser373, Ala372, Ser375, Asn437, Asn440, Ser375, ethyl chitosan in establishing efficient binding
and Phe374 (Figure 3). In addition, NMNC binds affinity against the S protein of SARS-CoV-2.
with ACE2 receptor at amino acids Asn397, In this context, the results of this computational
Ala396, Arg514, Glu398, Asp206, Gln102, Ser511, investigation indicate that the compounds listed
Tyr510, Trp203, Tyr199, Gly205, Tyr202, Tyr196, above can be considered for prospective antiviral
Glu208, Gln98, Leu95, Lys562, and Ala396. drugs against SARS-CoV2.
The bindings of mHTCC and NCMC with the A recent research demonstrated that silymarin-
RBD involve interactions such as conventional chitosan nanoparticles (Sil-CNPs) can act as a
hydrogen bonds, carbon-hydrogen bonds, potent antiviral agent for adenovirus 5 (ADV5)
unfavorable positive-positive interactions, alkyl and SARS-CoV-2. The researchers evaluated the
bonds, pi-sigma bonds, pi-pi T-shaped interactions, drug’s cytotoxic activity on Vero and Vero E6 cell
van der Waals interactions, and unfavorable donor- lines and found it non-cytotoxic while improving
donor interactions. Furthermore, the binding of its bioavailability and physicochemical qualities.
mHTCC and NCMC with ACE2 protein also The enhanced antiviral activity of Sil-CNPs may be
revealed the presence of conventional hydrogen attributed to their ability to inhibit the viral host ACE2
bonds, carbon-hydrogen bonds, unfavorable receptor, thus preventing the virus from attaching
positive-positive interactions, alkyl bonds, pi- to cells [33]. A separate study underscores the
alkyl bonds, pi-sigma bonds, alternative charges, reinforcement of bronchoalveolar lavage and local
salt bridges, van der Waals interactions, and mucosal immunity within the lungs, facilitated by
unfavorable donor-donor interactions. Similarly, the chitosan-mediated nanovaccine. This innovative
the ligands mHTCC and NCMC, when bound approach exhibits the capacity to strengthen the
to ACE2 sites, function as the region or medium host’s defense mechanisms against infection
responsible for the entry of the viral S protein. Our without causing systemic harm [34]. In addition,
findings also demonstrated strong binding of the chitosan/α-Ag WO 4 composites emerge as
2
ligands mHTCC and NCMC to the RBD site of the compelling agents with high efficacy in eliminating
S protein. Thus, the chitosan derivatives mHTCC pathogenic microorganisms, such as Escherichia
and NCMC demonstrated a dual role, strongly coli, methicillin-susceptible Staphylococcus aureus,
binding to the S protein and impeding viral entry and the yeast strain Candida albicans [35]. These
into the host cell ACE2 receptor. These findings composites also exhibit the ability to inactivate

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