![Molecular docking results of the COVID-19 spike protein and the ligands from the Ayurvedic preparation [4]](https://www.researchgate.net/publication/348356662/figure/tbl1/AS:985765827842048@1612036296756/Molecular-docking-results-of-the-COVID-19-spike-protein-and-the-ligands-from-the_Q320.jpg)
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R E S E A R C H Open Access
Compounds of Citrus medica and Zingiber
officinale for COVID-19 inhibition: in silico
evidence for cues from Ayurveda
M. Haridas
1*
, Vijith Sasidhar
2
, Prajeesh Nath
3
, J. Abhithaj
1
, A. Sabu
1
and P. Rammanohar
3
Abstract
Background: The nasal carriage of SARS-CoV-2 has been reported as the key factor transmitting COVID-19.
Interventions that can reduce viral shedding from the nasopharynx could potentially mitigate the severity of the
disease and its contagiousness. Herbal formulation of Citrus medica and Zingiber officinale is recommended in an
Ayurvedic text as a nasal rinse in the management of contagious fevers. These herbs are also indicated in the
management of respiratory illnesses and have been attributed with activity against pathogenic organisms in other
texts. Molecular docking studies of the phytocompounds of C. medica and Z. officinale were done to find out
whether these compounds could inhibit the receptor binding of SARS-CoV-2 spike protein (S protein) as well as the
angiotensin-converting enzyme 2 (ACE-2), as evidenced from their docking into binding/active sites.
Results: The proteins of SARS-CoV-2, essential for its entry into human cells and highly expressed in the goblet and
ciliated cells of nasal epithelium, play a significant role in contagiousness of the virus. Docking studies indicated
that the specific compounds present in C. medica and Z. officinale have significant affinity in silico to spike protein
of virus and ACE-2 receptor in the host.
Conclusion: In silico studies suggest that the phytochemical compounds in C. medica and Z. officinale may have
good potential in reducing viral load and shedding of SARS-CoV-2 in the nasal passages. Further studies are
recommended to test its efficacy in humans for mitigating the transmission of COVID-19.
Keywords: Ayurvedic formulation, COVID-19, SARS-CoV-2 spike protein, Angiotensin-converting enzyme 2, In silico
evidence
Background
The COVID-19 pandemic has become widespread, and
the total number of cases in the world has crossed the
seven million mark. Transmission of the disease by
asymptomatic individuals as well as increased transmis-
sion in health care settings is a matter of great concern.
A sudden spike in cases, especially severe presentations
of COVID-19, overwhelms the health care system. There
is a need to explore the potential of multiple
interventions in mitigating the transmission and severity
of COVID-19. Virus-infected symptomatic patients and
upper respiratory tract of SARS-CoV-2 patients with
high viral loads are the crucial factors contributing to its
high transmission [1]. Several research papers have rec-
ommended the use of different solutions for oropharyn-
geal wash and nasal irrigation as well as a steam
inhalation to reduce viral load in the oropharynx and
nasopharynx [2,3]. The Ayurvedic text Yogaratnākara
[4] prescribes a herbal formulation with Citrus medica
and Zingiber officinale for nasal cleansing in the context
of the treatment of sannipātajvara (fever caused by dis-
turbance of all three doṣas, the human groupings by
Ayurvedic constructs) [4].
© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
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licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
* Correspondence: mharidasm@rediffmail.com
1
Inter University Centre for Bioscience and Department of Biotechnology &
Microbiology, Dr Janaki Ammal Campus Thalassery, Kannur University,
Palayad 670661, India
Full list of author information is available at the end of the article
Future Journal of
Pharmaceutical Sciences
Haridas et al. Future Journal of Pharmaceutical Sciences (2021) 7:13
https://doi.org/10.1186/s43094-020-00171-6
In COVID-19, high titres of SARS-CoV-2 are detect-
able in the upper respiratory tract of asymptomatic and
symptomatic individuals. The proteins of SARS-CoV-2,
essential for its entry into human cells, are highly
expressed in the goblet and ciliated cells of the nasal epi-
thelium [1]. Analysis of saliva of COVID-19 patients at
the time of admission to the hospital revealed up to 1.2
× 108 infective copies/mL of the virus [5]. It has recently
been found that human nasopharynx has a higher viral
load than oropharynx [5,6].
A pilot randomised controlled study of hypertonic sa-
line for nasal irrigation and gargling to treat upper re-
spiratory tract infections in adults has been analysed
post hoc. The above treatment was found useful to a
subgroup with alpha and beta coronavirus infection, in
the reduction of disease symptoms and illness duration
[2]. Epithelial cells mount an antiviral effect with hypo-
chlorous acid (HOCl) produced from chloride ions.
Epithelial cells have the innate antiviral immune mech-
anism to clear viral infections. In the presence of chlor-
ide ions supplied via salt, enveloped or non-enveloped
DNA and RNA viruses were inhibited in epithelial cells
[7]. As an adjunct to personal protective equipment,
nasal spray and oropharyngeal wash with the povidone-
iodine solution in health care workers and patients have
been described to reduce the risk of COVID-19 spread-
ing [3]. Thus, the use of nasal cleansing solution has a
role to play in controlling the spread of COVID-19 and
mitigating severity of the disease.
S protein and ACE-2 are critical in cellular entry and
multiplication of SARS-CoV-2 found in COVID-19.
Host cell entry of the virus is prerequisite for infection.
During this process, S protein recognises host cell recep-
tors and induces viral and host cell membrane fusion.
It is found that the S protein of SARS-CoV-2 is similar
to the S protein of SARS-CoV [8]. Substantial structural
rearrangement of the S protein from its metastable pre-
fusion conformation to another distinct conformation is
required for the fusion of viral envelope with the host
cell membrane [9]. If this transformation is curtailed, the
virus will become unable to make cell entry and hence
cannot cause infection. The irregularly structured con-
nector of the receptor-binding domain (RBD) of S pro-
tein (S1) would act as a hinge to engage the cellular
membrane by drastic conformational movements. Any-
thing which hinders this process would disable the spike
protein to infect the host cell.
Consequently, it may be hypothesised that a viral neu-
tralising agent may have some constituent to bind onto
the RBD. The nasal rinse prepared from C. medica and
Z. officinale may likely have ligands with affinity to the
RDB capable of making the virus inefficient to infect the
host cell. It has been demonstrated that ACE-2 is
expressed mainly in alveolar epithelial cells. It is almost
absent in other lung cells and also in bronchial epithelial
cells, endothelial cells, fibroblasts, and macrophages [10].
Blocking of the renin-angiotensin signal pathway could
alleviate severe acute lung injury caused by SARS-CoV-2
S protein, which would otherwise lead to pathogenesis
facilitated by ACE-2 receptor [11–13]. An inhibitor of
ACE-2 enzyme would, therefore, inhibit the pathogen-
esis of the COVID-19.
Methods
The ligands
The herbal constituents of the solution mentioned in the
Ayurvedic classic for nasal and throat cleansing for the
symptoms similar to COVID-19 are cedrat (Citrus
medica) and ginger (Zingiber officinale)[4,14]. The
compounds rhoifolin, naringin, neohesperidin, apigenin
6,8-di-C-glucoside, adenine, hesperidin, 6-gingerol,
xanthin, 8-gingerol, scopoletin, isovanillin, 10-gingerol,
10-shogaol, 8-paradol, and 10-paradol present phenom-
enally in ginger and cedrat were selected (Figs. 1and 3)
[15,16].
The targets
The structure of spike glycoprotein showed as a single
polypeptide chain with 1300 amino acids forming a
homo-trimer and cleaved by furin-like proteases of the
host cell into SI and S2 subunit. S1 subunit is the N-
terminal domain which is responsible for the host cell
attachment by binding to the cell membrane receptors
through its receptor-binding domain, and S2 is the C-
terminal domain [17,18]. The receptor-binding domain
in the S1 subunit of the SARS-CoV-2 is therefore re-
sponsible for the zoonotic transmission, recognition of
host cell, and invasion. The S2 subunit comprises two
heptad regions (HR1 and HR2) and a lipophilic fusion
peptide and forms the coiled helix structure of the sub-
unit. During the process of infection, the RBD in the S
protein bound to the cell surface receptor would trigger
conformational change in the S1 and S2. As the conse-
quence of the RBD triggered conformational change,
fusion loop exposes and fuses to the membrane together
with the heptad region of the S protein, forming a bun-
dle fusion core. These orchestrated molecular move-
ments would facilitate the fusion of viral and host cell
membranes. A thorough understanding of the role of
ACE-2 and pathophysiological changes caused by the
virus in the human body may help discover and explain
the corresponding clinical phenomena.
Protein preparation and receptor grid generation
The downloaded PDB coordinates of SARS-CoV-2 S
protein and ACE-2 (6VSB and 1R4L, respectively) were
used to prepare the structure by protein preparation
wizard in the Maestro software (Maestro, v11.4,
Haridas et al. Future Journal of Pharmaceutical Sciences (2021) 7:13 Page 2 of 9
Schrodinger, LLC, NY). Since the ligand-bound structure
of spike protein was not readily available, the grid prep-
aration was based on the receptor-binding site residues
of the spike protein. In the pre-processing step, the het-
ero group having bond order and formal charges were
added, hydrogen atom was added to all the atoms in the
system, disulfide bond and zero-order bonds to metals
were created, and water molecule within 5 Å in the het-
ero groups was removed. Then, the structure refinement
step followed. The missing side-chain atoms were incor-
porated. Then for each structure, a brief relaxation was
performed with Impact Refinement module (Impref) in
order to remove the crystallographic bias. Here, an all-
atom constrained minimization was carried out with the
aid of forcefield OPLS_2005 to relieve steric clashes
present in the original PDB structure. Minimization job
will get terminated when the RMSD cutoff of 0.30 Å is
attained. Receptor grid was generated based on the bind-
ing site residues, where no bound ligand is present. The
receptor-binding site residues of SARS-CoV-2 spike pro-
tein are TYR449, TYR453, ASN487, GLY496, THR500,
GLY502, and TYR505. They were selected for grid gen-
eration [19]. ACE-2 grid generation was carried out by
selecting the centroid of XX5 (co-crystallised ligand of
PDB ID: 1R4L). The receptor grid generation was ac-
complished by receptor grid generation panel on the
GLIDE module of Maestro.
Ligand preparation
The ligands identified as described above were prepared
for using the LigPrep module with Epik to expand
protonation and tautomeric states at neutral pH (7 ± 1).
The energy minimization of ligands also carried out with
OPLS_2005 forcefield.
Molecular docking
In order to identify the nature of the interaction of the
selected compounds with the spike protein, molecular
docking was done. GLIDE (Grid-based Ligand Docking
with Energetics) module of Schrodinger suite was used
for molecular docking. The amino acids of the binding
site were mapped. A grid box was generated around the
site cavity with a size of 20 Å
3
. The results were
expressed based on the binding affinity and ranked by
GlideScores (G score), the ligand binding free energy.
The initial protocol employed for molecular docking was
the standard precision (SP) docking module of GLIDE.
Finally, the extra precision (XP) docking method was
used to identify the best hits. The G score obtained via
ligand-receptor interaction was calculated as imple-
mented in the GLIDE. Top-scoring phytochemicals were
subjected for binding free energy prediction by
MMGBSA method using Prime Module of the same
software.
Results
Phytocompounds showing good binding affinity towards
spike protein are shown in Fig. 1and for ACE-2 in Fig.
3. The GLIDE scores of the ligand molecules docked on
to the SARS-CoV-2 spike protein are listed in Table 1.
The binding energy of these compounds docked onto
the protein is calculated by the method Prime Module of
the same software which has been given as Table 2.
The GLIDE scores show the affinity of the docked
compounds to the binding site (ACE-2 receptor) of the
SARS-CoV-2 spike glycoprotein. Table 1lists eight com-
pounds in the decreasing order of the binding affinity to-
wards the spike protein. The lower-ranking compounds
Fig. 1 2D structures of COVID-19 spike protein ligands
Table 1 Molecular docking results of the COVID-19 spike
protein and the ligands from the Ayurvedic preparation [4]
Compound Plant GlideScore
Rhoifolin C. medica −7.361
Naringin C. medica −7.112
Neohesperidin C. medica −6.564
Apigenin 6,8-di-C-glucoside C. medica −6.409
Adenine Z. officinale −5.004
Hesperidin C. medica −4.791
6-Gingerol Z. officinale −4.177
Xanthin C. medica −4.063
Haridas et al. Future Journal of Pharmaceutical Sciences (2021) 7:13 Page 3 of 9
are omitted for convenience. The ranking was done on
the basis of GLIDE score, taking −5.00 kcal/mol as an
appropriate benchmarking critical score for the top-
scoring compounds namely rhoifolin, naringin, neohe-
speridin, and apigenin 6,8-di-C-glucoside. They showed
critical interaction with TYR453 which is an important
residue present in the RBD domain of spike protein.
Without reference to an experimental value of a stand-
ard inhibitor, it will be inappropriate to make a quantita-
tive statement on the behaviour of the SARS-CoV-2
spike glycoprotein binding molecule. However, it could
be understood that there are many compounds which
would bind to the SARS-CoV-2 spike glycoprotein and
would render it incapable of interacting with the host
cell membrane to initiate pathogenesis. Table 2also
shows an explanatory binding energy profile of the same
compounds towards the spike protein.
Apart from the protein binding free energies of top-
scoring phytocompounds, this table shows their contacts
to the protein. There are differences in the contact resi-
dues for different compounds. It is understood as their
chemical differences in interacting moieties.
Figure 2shows the protein-ligand interactions of all
the eight compounds taken up for study as surface
views. Also, the protein binding details of the top-
scoring compound have been shown as a molecular car-
toon. Protein-ligand interaction, at the receptor-binding
site of the protein, of rhoifolin having the highest GLIDE
score is shown in detail in the figure. Table 2gives the
details of interacting residues of the target protein with
rhoifolin.
The GLIDE scores of the ligand molecules docked on
to the ACE-2 are listed in Table 3. The binding energy
of these compounds docked onto the protein is calcu-
lated by the method Prime Module of the same software
which has been given as Table 4. Like in the previous
case of the spike protein-ligand interactions, the GLIDE
scores in the case of ACE-2 at its RBD show the affinity
of the docked compounds. Table 3lists eight com-
pounds in the decreasing order of the binding affinity
towards the ACE-2 receptor. The compound found co-
crystallised with ACE-2 was also considered for docking
exercise. The lower-ranking compounds are omitted for
convenience since they would tend to insignificance. It
may be seen that the compound, docked into the active
site of ACE-2 during co-crystallisation, ranks only as of
the lowest amongst the listed compounds. It shows that
all the other eight compounds may be more potent in-
hibitors to the ACE-2. It could be discerned that there
are many compounds which would bind to the ACE-2
and would render it inactive for the pathogenesis of
COVID-19 (Fig. 3). Figure 4shows the protein-ligand in-
teractions of all the eight compounds taken up for study
as surface views. Details of the protein binding with the
top-scoring compound have been shown as a molecular
cartoon. Protein-ligand interaction, at the active site
binding of the enzyme, of neohesperidin having the
highest GLIDE score is shown in detail in the figure.
Neohesperidin forms three H bonds with ASN51,
ALA348, and ASP350 present on the ACE-2 and has the
binding energy of −51.48 kcal/mol.
Discussion
The in silico evidence from our study suggests that the
Ayurvedic nasal purge [4] could inactivate the virally
transcripted S protein required for pathogenesis. Besides,
it also inhibits the ACE-2 receptor in the host cell. The
docking studies implicate that the mode of action of the
Ayurvedic nasal purge simulates the use of a subunit
vaccine by the mechanism of action lasting for a short
time.
The Ayurvedic text clarifies that by the use of this
nasal purge, the mucus secretions will flow out relieving
the afflictions of the head, chest, throat, mouth, and the
sides of the chest [4]. It indicates that the purpose of this
application is to protect the organs connected to the
upper respiratory passages and mitigate the severity of
the symptoms. Nasya is also recommended as a prevent-
ive practice as part of the daily routine for nasal hygiene.
Suśrutasamhitāalso advises the application of nasal
drops by a healthy person before going out of one’s
house into the public spaces [20].
Table 2 Spike protein binding free energies of top-scoring phytocompounds
Compound name H bonds Interacting residues Binding free energy
Rhoifolin 5 TYR453, SER494, TYR495, THR500 −58.43
Naringin 5 TYR453, SER494, TYR499, THR500 −44.48
Neoesperidin 5 TYR453, SER494, GLY494, GLY504 −60.95
Apigenin 6,8-di-C-glucoside 5 TYR449, TYR453, GLY496, GLY504 −37.87
Adenine 2 TYR495, GLY496 −24.18
Hesperidin 2 GLY496, TYR505 −59.47
6-Gingerol 4 TYR453, SER494, GLY496, TYR505 −38.60
Xanthin 1 TYR453 −18.26
Haridas et al. Future Journal of Pharmaceutical Sciences (2021) 7:13 Page 4 of 9
In the formulation used in our study, fresh ginger and
cedrat are the primary ingredients along with rock salt,
black salt, and ammonium chloride. The ionic salts may
help the absorption of the compounds present in the
medicinal preparation, essentially derived from the two
major plant materials mentioned above. This formula-
tion is used for cleansing the nasal passages to obtain re-
lief from symptoms of sannipātajvara. Certain other
citrus fruits also could be used to treat cough and dys-
pnoea, and cleanse the throat, tongue, and heart [21]. Its
ability to clear the nasopharynx and oropharynx has also
been emphasised in anther classic text [22]. Also, it is at-
tributed to antimicrobial and anti-inflammatory activity
[23]. Ginger has been attributed to the anti-
inflammatory activity. It is also indicated for the
management of respiratory disorders like dyspnoea and
cough [24]. The phytocompounds in this formulation
will likely have benefit in reducing the severity of
COVID-19 by inhibiting SARS-CoV-2 in the nasal pas-
sages. Such a formulation would be relevant for applica-
tion in individuals with high-risk exposure as well as
COVID-19 patients who are asymptomatic or have mild
symptoms to mitigate the transmission of SARS-CoV-2.
We examined in silico target binding behaviour of the
major phytochemical components of both ginger and
cedrat to find out if they could inhibit the critical treat-
ment targets of COVID-19, the spike protein and the
ACE-2 receptor. Besides the above hypothesis, the
hypertonic saline solution and fresh ginger juice also
have antiviral activity [24]. Effects of fresh and dried
Fig. 2 Docked postures of the phytocompounds onto the receptor-binding site of the SARS-CoV-2 spike glycoprotein
Haridas et al. Future Journal of Pharmaceutical Sciences (2021) 7:13 Page 5 of 9
ginger hot water extracts on HRSV, in human upper
(HEp-2) and lower (A549) respiratory tract cell lines,
were tested by plaque reduction assay [25]. The ability of
ginger to stimulate antiviral cytokines was evaluated by
ELISA [14]. Fresh, but not dried, ginger is effective
against HRSV-induced plaque formation on airway epi-
thelium by blocking viral attachment and internalisation
[25]. However, the above studies reporting positive re-
sults of the antiviral effect of ginger have not explained
the mechanism of action at the level of molecular inter-
actions. As hypothesised, the compounds present in
ginger and cedrat may have neutralising effect on SARS-
CoV-2 by inhibiting the spike glycoprotein in the virus
and the enzyme ACE-2 in the host, both being crucial
factors enabling cell entry of SARS-CoV-2. As a prelim-
inary step to test this hypothesis, the interactions at the
active/binding site of the SARS-CoV-2 with the phyto-
compounds present in ginger and cedrat by molecular
docking were studied.
Chang et al. [25] have shown that only fresh ginger
inhibited human respiratory syncytial virus-induced
plaque formation in HEp-2 and A549 cell lines dose-
dependently. They have shown that fresh ginger
inhibited viral attachment and internalisation dose-
dependently. Fresh ginger of high concentration could
stimulate mucosal cells to secrete interferon-βthat
possibly contributed to counteracting viral infection.
Fresh ginger stimulates secretions more effectively
compared to dry ginger [14]. Also, Greño et al. [26]
have demonstrated that Citrus medica also has some
antiviral properties. However, these are not explained
in molecular terms. The molecular mechanism of
antiviral property of certain compounds found in gin-
ger and cedrat has been demonstrated here in silico.
It may also be noted that there may be other bio-
logical mechanisms underlying the antiviral action of
the medicinal preparations containing ginger and
cedrat. It is not clear whether the compounds in the
Ayurvedic formulation [4] discussed above will enter
the systemic circulation or other areas in the upper
and lower respiratory tracts. It is quite possible that
the well-known anti-inflammatory activity of ginger
may also have a role in giving relief from symptoms
of ‘sannipatajvara’in the head, oral cavity, throat, and
chest as claimed in the Yogaratnakara [4]. Further
studies exploring such activities of the formulation as-
sume relevance in the present context of COVID-19.
As ginger in higher doses can irritate the mucous
membranes, the dosage and dilution of the formula-
tion must be optimised. Especially, the combination
of ginger has been contraindicated in skin diseases, in
bleeding disorders, and in summer. These contraindi-
cations also apply to salt [22].
There are limitations to this study, and the in silica
evidence needs to be substantiated by possible in vitro
and human clinical studies. Before human studies, the
formulation has to be standardised. As the formulation
contains ingredients like ginger, the possibility of insults
to the delicate nasal epithelium must be kept in mind
while optimising the dosage.
Table 4 Binding free energies of top scored compounds and control at the active site of ACE-2
Compound name No. of H bonds Interacting residues Binding free energy
XX5* 3 ASP367, LYS363, ASN368 −31.39
Neohesperidin 3 ASN51, ALA348, ASP350 −51.48
Hesperidin 4 TRP203, ASN394, SER511 −59.87
10-Paradol 2 ARG273, LYS363 −37.87
8-Paradol 3 ASN149, LYS363 −51.27
Scopoletin 3 ASN149, ASN368, LYS363 −40.32
10-Shogaol 3 ASN277, LYS363, ASP367 −44.61
8-Gingerol 3 ASP367, LYS363 −46.85
10-Gingerol 2 GLU406, ARG518 −33.72
Table 3 Molecular docking results of the ACE-2 and the ligands
from the Ayurvedic preparation [4] and the co-crystallised
compound
Compound Plant GlideScore
XX5* Standard −4.36
Neohesperidin C. medica −9.94
Hesperidin C. medica −8.28
10-Paradol Z. officinale −6.11
8-Paradol Z. officinale −4.76
Scopoletin Z. officinale −4.73
10-Shogaol Z. officinale −4.70
8-Gingerol Z. officinale −4.69
10-Gingerol Z. officinale −4.56
XX5*—(S,S)-2-{1-Carboxy-2-[3-(3,5-Dichloro-Benzyl)-3h-Imidazol-4-Yl]-
Ethylamino}-4-Methyl-Pentanoic Acid
Haridas et al. Future Journal of Pharmaceutical Sciences (2021) 7:13 Page 6 of 9
Conclusion
In the absence of a vaccine, the contagiousness of SARS-
CoV-2 virus is a matter of primary concern. COVID-19
pandemic continues to spread across the length and
breadth of the world. The use of an ancient, time-tested
formulation for nasal cleansing could play an important
role in mitigating the contagiousness of SARS-CoV-2 by
inhibiting the multiplication and shedding of the virus in
the nasal epithelium. Administration of this nasal purge
may be especially relevant in people with high-risk ex-
posure to COVID-19 patients like frontline workers and
health care professionals. It could also be helpful in
asymptomatic patients and patients with mild symptoms
in the early stages of the disease, when viral shedding
Fig. 3 2D structures of ACE-2 ligands (2D structures of hesperidin and neohesperidin are shown in Fig. 1)
Fig. 4 Docked postures of the phytocompounds onto the active site of the ACE-2
Haridas et al. Future Journal of Pharmaceutical Sciences (2021) 7:13 Page 7 of 9
and contagion are highest. It may be summed up that
the administration of nasal purge could be considered
for in vitro studies and human trials for mitigating trans-
mission and severity of COVID-19. As demonstrated in
silico, most of the major chemicals found in cedrat and
ginger do interact at the active sites of the RBD of
COVID-19 spike protein and human ACE-2, to elicit
antiviral property and inhibit spreading of COVID-19
disease. This would become an ideal home remedy for
COVID-19 disease in the present context.
Abbreviations
SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-
19: Coronavirus disease 2019; ACE-2: Angiotensin-converting enzyme 2;
HOCl: Hypochlorous acid; RBD: Receptor-binding domain; S protein: Spike
protein; HR1 and HR2: Heptad regions 1 and 2; PDB: Protein Data Bank;
RMSD: Root mean square deviation; GLIDE: Grid-based Ligand Docking with
Energetics; G score: GlideScores; SP: Standard precision; XP: Extra precision
Acknowledgements
No specific acknowledgement
Declaration on referenced materials
The herbal constituents of the solution mentioned in the manuscript, as in
the Ayurvedic classic for nasal and throat cleansing are cedrat (Citrus medica)
and ginger (Zingiber officinale). Ginger is an extensively cultivated farm
product, and cedrat is a citrus variety grown in medicinal gardens. The
compounds are from references [15,16] for the Citrus medica and Zingiber
officinale, respectively, which are authenticated in references [15,16].
Authors’contributions
MH pioneered in developing the hypothesis, planned the work, interpreted
the data, written the manuscript, and corresponded; VS contributed in
developing the hypothesis, interpreting the data, and preparing the
manuscript; PN contributed in developing the hypothesis, interpreting the
data, and preparing the manuscript; JA performed the in silico work; AS
contributed in developing the hypothesis, interpreting the data, and
preparing the manuscript; PR involved in developing the hypothesis,
planned the work, interpreted the data, and co-written the manuscript. All
authors have read and approved the manuscript.
Funding
No specific funding was obtained for this study from any governmental or
non-governmental agencies.
Availability of data and materials
All data generated or analysed during this study are included in this
published article [and its supplementary information files].
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
Inter University Centre for Bioscience and Department of Biotechnology &
Microbiology, Dr Janaki Ammal Campus Thalassery, Kannur University,
Palayad 670661, India.
2
Sree Krishna Ayurveda Chikitsa Kendram, Vaikom,
Kerala, India.
3
Amrita School of Ayurveda, Amrita Vishwa Vidyapeetham,
Kollam, Kerala, India.
Received: 24 September 2020 Accepted: 26 December 2020
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