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37 INNOSC Theranostics and Pharmacological Sciences, 2022, Vol. 5, No. 2 Das et al.
3.2. Molecular docking Waals interactions, and unfavorable donor-donor
interactions. Figure 2 illustrates the 2D interaction of
3.2.1. Interaction of different monomeric subunits mHTCC with the S protein.
of chitosan with the S protein
3.2.3. Interaction studies of NCMC with the S
The binding modes of monomeric units of protein
chitosan and its derivative with the S protein
were investigated using AutodockVina1.1.2. The binding affinity exhibited by NCMC toward
The free binding energies (ΔGb) of the S protein the S protein was found to be the highest, followed
with energy-minimized chitosan monomeric by carboxy ethyl chitosan, with binding energies of
and polymeric units, as well as its derivative, −7.9 and −7.2 kcal/mol, respectively. Nevertheless,
namely, mHTCC, N,O-carboxymethyl chitosan, the binding affinity of NCMC with the S protein was
glycerol chitosan, methyl methacrylate chitosan, even higher than that exhibited by mHTCC, involving
monomeric chitosan, NCMC, carboxy ethyl the participating amino acids, namely, Ala1016,
chitosan, N-octadecanoyl-N-3-carboxy propionyl Ala1016, Glu1017, Glu1017, Glu1017, Arg1019,
chitosan, and palmitoyl-trimethyl-chitosan, were Arg1019, Ala1020, Ala1020, Ser1021, Asn1023,
calculated as −6.2, −5.9, −4.9, −5.3, −7.9, −7.2, Asn1023, Leu1024, Leu1024, Thr1027, Thr1027,
−6.4, and −6.9 kcal/mol, respectively. Further Glu1031, Phe1042, Phe1042, Ala1016, Ala1020,
information on the type of modification, solubility Asn1023, Leu1024, Thr1027, Arg1039, Arg1039,
parameters, molecular mass, antiviral spectrum, Arg1039, and Arg1039. Further investigation into
and mechanism of action of the selected chitosan the binding energy of NCMC involved its interaction
derivatives can be found in Figures 2, 3, and with the RBD of the S protein and ACE2 receptor.
S2–S7. Table 2 provides a brief elaboration on the The binding affinity of NCMC for the RBD of the S
binding energy, interacting amino acids of the S protein was found to be -6.3 kcal/mol, involving the
protein, and the type of interaction with the selected participating amino acids, such as Asn343, Arg509,
chitosan derivatives. The 2D interaction between Thr345, Ala344, Leu441, Trp436, Asp442, Ser438,
the S protein and the selected chitosan derivatives Ser373, Ala372, Ser375, Asn437, Asn440, Ser375,
is provided in Figures 2, 3, and S2–S7. and Phe374. Similarly, NCMC binding to ACE2
receptor exhibited binding energy of −7.4 kcal/mol,
3.2.2. Interaction studies of mHTCC with the S with primary participating amino acids including
protein Asn397, Ala396, Arg514, Glu398, Asp206, Gln102,
The mHTCC unit exhibits specific interaction with the Ser511, Tyr510, Trp203, Tyr199, Gly205, Tyr202,
S protein, particularly at the RBD site of the S protein Tyr196, Glu208, Gln98, Leu95, Lys562, and Ala396.
and ACE2 receptor, with binding affinities recorded These interactions involved conventional hydrogen
as −6.2, −4.8 and −5.5 kcal/mol, respectively. The bonds, carbon-hydrogen bonds, unfavorable
present investigation elucidates that HTCC directly positive-positive interactions, alkyl bonds, pi-alkyl
binds with certain amino acids of the S protein, bonds, pi-sigma bonds, alternative charges, salt
including Glu1017, Ala1016, Ile1013, Thr961, bridges, van der Waals interactions, and unfavorable
Gln762, Ala958, Gln954, Arg1019, Arg1014, donor-donor interactions (data not provided).
Gln954, Gln1010, Gln954, Arg765, and Leu1012, Figure 3 illustrates the 2D interaction of NCMC
and those presented in the RBD, such as Ser438, with the S protein, the RBD of the S protein, and the
Asp442, Phe342, Ala344, Asn440, Asn343, Asn437, ACE2 receptor, as well as participating amino acids
Thr345, Trp436, Leu441, and Leu441. In addition, at the RBD and ACE2 receptor, and the binding of
interactions with the ACE2 receptor involve Lys562, NCMC with the S protein.
Tyr196, Gln102, and Ala99 (data on the interactions 3.3. Protein-protein interaction
with the ACE2 receptor are not provided). These
interactions primarily involve conventional hydrogen The best ten docking models with different free
bonds, carbon-hydrogen bonds, unfavorable energies were obtained from the ClusPro web server,
positive-positive interactions, alkyl bonds, pi- using the total root mean square deviation value as
sigma bonds, pi-pi T-shaped interactions, van der the grouping criteria [29]. From these models, we

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