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Phytochemical 6-Gingerol -A promising Drug of choice for COVID-19

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Int. J. Adv. Sci. Eng. Vol.6 No.4 1482-1489 (2020) 1482 E-ISSN: 2349 5359; P-ISSN: 2454-9967
Thirumalaisamy Rathinavel et al.,
International Journal of Advanced Science and Engineering
Phytochemical 6-Gingerol A promising Drug of choice
for COVID-19
Thirumalaisamy Rathinavel1, Murugan Palanisamy2,
Srinivasan Palanisamy1, Arjunan Subramanian*1, Selvankumar Thangaswamy*1
1Department of Biotechnology, Mahendra Arts & Science College (Autonomous),
Namakkal (Dt) -637 501, Tamil Nadu, India
2Nichi Asia Life Sciences Sdn Bhd, Kota Damansara, Malaysia
Corona virus is the group of viruses that have a
crown-like appearance when viewed under the
electronic microscope. Corona viruses cause
respiratory tract infections in humans, which can
cause a wide range of illnesses from the mild
common cold to lethal SARS and MERS. There are no
vaccines and anti-viral drugs are available yet to
treat corona viral infections. Corona virus possesses
positive sense single-stranded enveloped RNA as
their genetic material. The genome of corona virus is
the largest group among the viruses is host specific
which is based on the receptor specificity of their S-
Protein. It is an enveloped virus that is made up of
In December 2019, the novel corona virus
(2019-nCoV or SARS CoV-2), cause corona virus
disease 2019 (COVID-19) in humans, was an
outbreak in Wuhan, China. The epidemic disease of
SARS CoV-2 in Wuhan has occurred human to human
transmission among close contacts, which becomes
emerged as a pandemic disease from January 2020
spread through international travelers across the
different countries and enters almost all the
countries except few of them. As of 10th April 2020,
there have been over 1.6 million cases with over 0.1
million deaths for the COVID-19 outbreak worldwide
[1] However, there are currently no effective
medications against SARS CoV-2. Several national
and international research groups are working on
the development of vaccines to prevent and treat the
SARS CoV-2, but effective vaccines are not available
yet. There is an urgent need for the development of
effective prevention and treatment strategies for
SARS CoV-2 outbreak. Indian people are consuming
Indian traditional medicinal herb extract and Indian
spices to boost the immune system to fight COVID -
Ginger (Zingiber officinale) is the herbaceous
plant native to South Asia belonging to the family of
Zingiberaceae. The characteristic pungent flavor of
the ginger rhizome is used extensively in foods and
beverages [2]. Ginger is a common Indian spice and
traditional medicinal plants have important
pharmacologic activities such as antibacterial,
antiviral, anti-hypertensive, antioxidant, analgesic
and antipyretic properties [3]. Ginger has been
proved to be effective on various viruses [4-8].
Ginger rhizome possesses several outstanding
bioactive non-volatile phenolic compounds such as
gingerols, paradols, shogaols, and zingerones [9].
Ginger is one of the best choices of bioactive Phyto-
compound in traditional medicine in Ayurvedic,
Chinese and Unani systems to treat different diseases
in ancient times.
6-gingerol is a bioactive phenolic
phytocompound found in the fresh ginger rhizome.
6-gingerol is a promising drug candidate to treat
various diseases associated with inflammation,
ABSTRACT: Recently, a novel corona virus (COVID-19), identified as one of the acute respiratory syndrome
corona virus (SARS CoV-2) and emerged as a pandemic disease in Asia and European countries in 2020. The
World Health Organization (WHO) has declared the current outbreak as a global public he alth crisis. Due to the
variability in the amino acid and amino acid sequences, it does not develop suitable vaccines against the viral
proteins. Hence, the inhibitor to be developed against the viral proteins of the corona virus is a promising idea to
develop structure-based drugs from the photochemical compounds. Here, the novel drug was identified and well
studied against the viral receptors by using the molecular docking technique. Phytocompound 6-gingerol
possesses excellent drug likeliness with zero violations and very good pharmacokinetic properties with the
highest binding affinity ranging from -2.8764 KJ/mol to -15.7591 KJ/mol with various COVID-19 viral protein
targets. Our study reveals that 6-gingerol from ginger could act as a promising drug of choice to treat COVID-19.
KEYWORDS: SARS-CoV-2; COVID-19; 6-Gingerol, corona virus; respiratory infection. © 2020, All rights reserved
*Corresponding Authors: &
Received: 18.01.2020 Accepted: 21.03.2020 Published on: 18.04.2020
Int. J. Adv. Sci. Eng. Vol.6 No.4 1482-1489 (2020) 1483 E-ISSN: 2349 5359; P-ISSN: 2454-9967
Thirumalaisamy Rathinavel et al.,
International Journal of Advanced Science and Engineering
cancer, and viral disease. Fresh ginger possesses
anti-viral activity against human respiratory
syncytial virus due to the presence of bioactive
phenolic phytocompound 6-gingerol [10]. Hence, the
present study aims to examine phytocompound 6-
gingerol from the ginger plant (Zingiber officinale)
that could act as a promising drug against COVID-19
proteins and screened through in silico approach.
1.1. Ligand generation
The 2D structure of Zingiber officinale
phytocompound 6-gingerol (CID 442793) was
retrieved from Pubchem, a database of chemical
molecules [11]. The retrieved 2D SDF file format of
6-gingerol was submitted to “Online SMILES
convertor and Structure file generator‟ [12] and
converted into 3D SDF format.
1.2. Drug Likeliness and Absorption,
Distribution, Metabolism, Extraction and
Toxicity [ADME] Calculations
Swiss ADME online server was used to calculate
Drug Likeliness parameters. Drug likeliness of the
phytocompounds gingerol was examined based on
Violations of the following rules such as Lipinski,
Ghose, Veber, Egan, and Muegge. Pharmacokinetic
properties of phytocompounds gingerol were
screened by preADMET is a web-based application to
determine the pharmacological efficiency of
phytocompounds. PreADMET predicts the various
parameters associated with ADME and toxicity
behavior of phytocompounds.
1.3. Preparation of Receptor and its Binding Site
Novel corona viral (SARS-CoV-2 or COVID-19)
Proteases, Spike protein, RNA binding protein, N-
terminal RNA binding domain are the key viral
molecules involved in attachment and replication
and reproduction of viral particle in the human host
cells. These Protein target molecules served as a
novel target to inhibit the viral lifecycle in human
host cells. Three-dimensional structures of SARS
CoV-2 nine molecules of main proteases (5R7Y,
5R80, 5R81, 5R83, 5R84, 6LU7, 6LVN, 6M03, 6Y84),
one spike protein (6VSB), one RNA binding protein
(6W4B) and one N-terminal binding domain (6M3M)
was retrieved from RCSB PDB database
( [13].To determine the
binding affinities between the ligand and receptor,
the amino acids with the binding pockets were
predicted at the Q-site finder server [14].
1.4. Flexible docking
The generated gingerol SDF structures were
docked with the predicted binding site of all selected
protein target binding site by using teaching version
of FlexX [15] with following parameters i) default
general docking information ii) base placement using
triangle matching, iii) scoring of full score
contribution and threshold of 0.70 iv) Chemical
parameters of clash handling values for protein-
ligand clashes with maximum allowed overlap
volume of 2.9 A03 and intra-ligand clashes with clash
factor of 0.6 and considering the hydrogen in
internal clash tests. v) Default docking details values
of 200 for both the maximum number of solutions
per iteration and a maximum number of solutions
per fragmentation.
1.5. Prediction of ligand-receptor interactions
The interactions of phytocompound gingerol
with twelve SARS CoV-2 proteins targets in the
docked complex were analyzed by the pose-view of
LeadIT [16]. 2D and 3D pose view of SARS COV-2
protein target-phytocompound gingerol was
generated and analyzed using LeadIT.
1.6. Density Functional Theory DFT Analysis
DFT calculation for phytocompound gingerol
was performed using Gaussian 09 software. DFT
used to calculate HOMOLUMO orbital providing
energy gap between highest occupied molecular
orbital (HOMO) and lowest unoccupied molecular
orbital (LUMO) providing high and low electron
density regions on the compounds.
2.1. Drug Likeliness and ADME Calculation
Drug likeliness calculation for phytocompound
gingerol was made in Swiss ADME server and
revealed that 6-gingerol possess a molecular weight
of 294.39 g/mol, the number of hydrogen bond
acceptor and donor are 4 & 6 respectively. Gingerol
also possess excellent TPSA(topological polar surface
area), lipophilicities (iLog P) and water solubility
(Log S ESOL) values of 66.76, 3.48 & -2.96
respectively which proved there are nil (zero)
violations for drug likeliness rules such as Lipinski,
Ghose, Veber, Egan, and Muegge essential for better
drug likeliness properties
ADME property of gingerol calculated by
preADMET web-based application revealed that very
good pharmacokinetic properties such as absorption,
bioavailability and distribution parameters of 6-
gingerol such as HIA 86.75%, the pure water
solubility of 0.3460 mg/ml, 100% plasma protein
binding, which are tabulated and presented in Table
Figure 1- 2D & 3D structures of 6-Gingerol
Int. J. Adv. Sci. Eng. Vol.6 No.4 1482-1489 (2020) 1484 E-ISSN: 2349 5359; P-ISSN: 2454-9967
Thirumalaisamy Rathinavel et al.,
International Journal of Advanced Science and Engineering
Table 1 - ADME properties of 6-gingerol from
ginger plant
Human intestinal absorption (HIA, %)
Caco-2 cell permeability (nm/sec)
MDCK cell permeability (nm/sec)
skin permeability (logKp, cm/hour)
Buffer solubility (mg/ml)
Pure water solubility (mg/ml)
Plasma protein binding (%)
Blood-brain barrier penetration
2.2. Docking Study
Different COVID-19 target proteins (proteases,
spike protein, RNA binding protein) and their
docking score and 3D pose with 6-gingerol are
presented in Table 2 and their detailed molecular
interaction between them is tabulated and presented
in Table 3 & Figure 2.
The results of a flexible docking study by flexX
software between COVID-19 viral targets and
gingerol was exhibit the binding affinity and docking
score ranging from -2.8764 KJ/mol to -15.7591
KJ/mol. Gingerol exhibit the highest binding affinity
(-15.7591 KJ/mol) with 5R7Y COVID-19 main
protease essential for replication and reproduction
of SARS Cov-2. Corona Viral protease 5R7Y residues
such as His 164, Glu166, Thr190, Gln192 from
hydrogen-bonded interaction with phytocompound
gingerol, it also forms form non bonded interaction
with the residues of His164, Met 165, Glu166,
Leu167, Pro168, Arg188, Gln189, Thr190.
Gingerol exhibits binding affinity of -11.4082
KJ/mol, -12.9523 KJ/mol and -12.8835 KJ/mol with
COVID-19 viral RNA binding protein (6W4B), N-
Terminal RNA Binding Protein (6VSB), Spike
glycoprotein (6M3M) respectively. Molecular
interaction between COVID-19 viral spike
glycoprotein with Gingerol forms hydrogen-bonded
interaction with Glu63, Arg89, Thr92, Asp129
residues and form non bonded interaction with
Glu63, Lys66, Arg89, Thr92, Leu168, Pro169
residues of COVID-19 spike glycol protein.
Molecular interaction between COVID-19 viral
RNA binding protein with Gingerol makes hydrogen
bonded interaction with Val42, Pro58, Ser60, Thr68
residues and form non bonded interaction with
Arg40, Phe41, Val42, Phe57, Pro58, Lys59, Ser60,
Ile66, Thr68, Ile92 residues of COVID-19 spike glycol
The previous study reported that several
phytocompounds of flavonoids and phenolic
substances possess antiviral activities [17-19]
especially 6-gingerol possess antiviral activities. Siti
Khaerunnisa et al. [20] reported that 6-gingerol
binds with the COVID-19 main protease active sites
with the binding affinity of -5.40 K.Cal/mol.
Table 2 . COVID-19 Proteins Targets and its 3D Docking Pose with 6-gingerol
Protein 3D Structure
Crystal Structure of
COVID-19 main
protease in
complex with
Crystal Structure of
COVID-19 main
protease in
complex with
Int. J. Adv. Sci. Eng. Vol.6 No.4 1482-1489 (2020) 1485 E-ISSN: 2349 5359; P-ISSN: 2454-9967
Thirumalaisamy Rathinavel et al.,
International Journal of Advanced Science and Engineering
Crystal Structure of
COVID-19 main
protease in
complex with
Crystal Structure of
COVID-19 main
protease in
complex with
Crystal Structure of
COVID-19 main
protease in
complex with
COVID-19 main
protease in
complex with an
inhibitor N3
Structure of the
2019-nCoV HR2
The crystal
structure of
COVID-19 main
protease in apo
Int. J. Adv. Sci. Eng. Vol.6 No.4 1482-1489 (2020) 1486 E-ISSN: 2349 5359; P-ISSN: 2454-9967
Thirumalaisamy Rathinavel et al.,
International Journal of Advanced Science and Engineering
protein N-terminal
RNA binding
Prefusion 2019-
nCoV spike
glycoprotein with a
single receptor-
binding domain up
Nsp9 RNA binding
protein of SARS
SARS-CoV-2 main
protease with
unliganded active
site (2019-nCoV,
disease 2019,
2.3. DFT Study
DFT study is used to explain the accurate
structural and electronic properties of
phytocompounds. The electronic distribution
phytocompound 6-gingerol could provide a clear
picture of SARS CoV-2 protein-gingerol interactions,
which will be useful to explore the inhibition
potentials of the phytocompound 6-gingerol. HOMO
and LUMO orbital energies of 6-gingerol are shown
in Figures 3 & 4. The calculated various HOMO-
LUMO orbital energies are presented in Table 4.
The localization of HOMO and LUMO orbitals in
the compound is very important in intermolecular
interactions with SARS CoV-2 protein targets. 6-
gingerol (-0.20606eV, 0.10303eV, and 9.3187eV)
showed more stability and biological activity as it
shows less energy gap, low hardness, and more
softness. Thus the DFT calculations performed here
better evidence highest binding affinity of 6-gingerol
with SARS CoV-2 protein targets in molecular
Similar comparative DFT study of phytochemical
constituents of present in the bark extract of Ficus
racemosa β-Amyrin (-0.06277eV, 0.031385eV and
31.86235eV) showed more stability and biological
activity as it shows less energy gap, low hardness,
and more softness followed by Betulinic acid (-
0.23987eV, 0.119935eV and 8.33784eV) and
Stigmasterol (-0.26925 eV, 0.134625 eV and 7.42804
eV) [21]. It was possible to characterize the
compounds as well as their characteristics of
electron donor/electron acceptor compared with
other biological properties of the phytocompound by
DFT analysis.
Int. J. Adv. Sci. Eng. Vol.6 No.4 1482-1489 (2020) 1487 E-ISSN: 2349 5359; P-ISSN: 2454-9967
Thirumalaisamy Rathinavel et al.,
International Journal of Advanced Science and Engineering
Table 3 .Molecular interaction of 6-gingerol with different COVID-19 Protein targets
Target PDB
Gingerol and COVID-19 Target Protein Interactions
Hydrogen-Bonded Interactions
Non-Bonded Interactions
His 164, Glu166, Thr190, Gln192
His 164, Met 165, Glu166, Leu167, Pro168, Arg188,
Gln 189, Thr190
Phe 219, Asn 221, Asn 277, Arg 279
Trp218,Trp219, Asn221, Glu270, Leu271, Asn274,
Asn277, Arg279
Met6, Phe8,Pro9, Ile152, Tyr154, Arg298, Val 303,
Thr25, His41, Ser46, Gly143
Ile200,Val202,Glu240,Ile249, Phe294
Glu63, Arg89, Thr92, Asp129
Glu63, Lys66, Arg89, Thr92, Leu168, Pro169
Gln773, Gln954, Ile1013, Arg1019
Glu773, Gln954, Ile1013, Arg1014, Glu1017,
Val42, Pro58, Ser60, Thr68
Arg40, Phe41, Val42, Phe57, Pro58, Lys59, Ser60,
Ile66, Thr68, Ile92
Met6, Ile152, Tyr154
Met6, Phe8, Pro9, Ile152, Tyr154, Arg298, Gln298,
Val303, Thr304
(a) (b)
Figure 2 Interaction plot for 6-Gingerol with
COVID-19 Protein Targets (a-l)
a).Interaction of Gingerol with 5R7Y (-15.7591
KJ/mol) b).Interaction of Gingerol with 5R80
(-7.0885 KJ/mol)
(C) (d)
C).Interaction of Gingerol with with 5R81
d).Interaction of Gingerol with with 5R83
(e) (f)
e).Interaction of Gingerol with 5R84
f).Interaction of Gingerol with 6LU7
(g) (h)
g).Interaction of Gingerol with 6LVN
h).Interaction of Gingerol with 6M03
(-8.6837 KJ/mol)
Int. J. Adv. Sci. Eng. Vol.6 No.4 1482-1489 (2020) 1488 E-ISSN: 2349 5359; P-ISSN: 2454-9967
Thirumalaisamy Rathinavel et al.,
International Journal of Advanced Science and Engineering
(i) (j)
(i)Interaction of Gingerol with 6M3M
(-12.9523 KJ/mol)
(j)Interaction of Gingerol with 6VSB
(k) (l)
(k)Interaction of Gingerol with 6W4B
(-11.4082 KJ/mol)
(l)Interaction of Gingerol with 6Y84
(-9.7625 KJ/mol
Figure 3 . HOMO orbital energy for 6-Gingerol
Figure 4.LUMO orbital energy for 6-Gingerol
The present study was attempted to prove that
phytocompound 6-gingerol from Zingiber officinale
acts as a promising drug to treat COVID-19. 6-
Gingerol possesses excellent drug likeliness
parameters with zero violations of different rules
and very good ADME pharmacokinetic properties.
Finally, 6-gingerol proves anti-viral efficiency against
SARS CoV-2 by showing the highest binding affinity
and interaction with multiple targets of COVID-19
including Viral proteases, RNA binding protein, Spike
protein. DFT study finally evidences the reason
behind the highest binding affinity between 6-
gingerol and COVID-19 protein targets. The present
study proves that 6-gingerol from the ginger plant
could be served as a promising drug to treat the
novel COVID-19.
This work is partially supported by the PG &
Research Department of Biotechnology, Mahendra
Arts and Science College (Autonomous), and the
Department of Science and Technology, Government
of India (DST-FIST sponsored - Ref. No.
Table.4. HOMO LUMO Orbital Energies for 6-
Gingerol through DFT calculations
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... Consistent with molecular docking analyses, 6-gingerol was also found to exhibit high binding affi nity with a number of virus proteins (major protease, SARS-CoV3C-like molecule, and cathepsin K) that are essential for the SARS-CoV-2 replication [41]. 6-gingerol also binds to protein S and several RNA-binding proteins of SARS-CoV-2 [42]. Docking analyzes also revealed that gingerol, geraniol, shogaol, zingiberene, zingiberenol, and zingerone interact with key residues in the catalytic domain of MPro [43]. ...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects other systems, including the digestive, circulatory, urogenital, and even the central nervous systems, as its receptor Angiotensin-Converting Enzyme-2 (ACE-2) is expressed in several organs, such as lungs, intestine, heart, esophagus, kidneys, bladder, testes, liver and brain. Different mechanisms, in particular, massive virus replication, extensive apoptosis and necrosis of lung-related epithelial and endothelial cells, vascular leakage, hyperinflammatory responses, overproduction of proinflammatory mediators, cytokine storm, oxidative stress, the downregulation of ACE2 and impairment of the renin-angiotensin system contribute to the pathogenesis of COVID-19. Currently, COVID-19 is a global pandemic with no specific antiviral treatment. The favorable abilities of ginger were indicated in patients suffering from osteoarthritis, neurodegenerative disorders, rheumatoid arthritis, type 2 diabetes, respiratory distress, liver diseases, and primary dysmenorrhea. Ginger or its compounds exhibited strong anti-inflammatory and antioxidant influences in numerous animal models. This review provides evidence regarding the potential effects of ginger against SARS-CoV-2 infection and highlights its antiviral, anti-inflammatory, antioxidant, and immunomodulatory impacts in an attempt to consider this plant as an alternative therapeutic agent for the treatment of COVID-19.
... Besides this it was found to be effective against HRSV (Human respiratory syncytial virus)-induced infection in two cancer cell lines: A549 and Hep-2 (Chang et al., 2013). 6gingerol obtained from ginger may act as a promising phytocompound for drug discovery to combat COVID-19 as it shows the maximal binding affinity with manifold targets of SARS-CoV-2 such as viral protease and RNA binding protein (Rathinavel et al., 2020). Zingiber officinale gives rise to phytochemical compounds that have a very good potential to reduce the viral load and shedding of SARS-CoV-2 in the nasal passages (Haridas et al., 2021). ...
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... 6-Gingerol and eugenol, two other metabolites present in DSV, are shown to have a high binding affinity for M pro active sites. Apart from SARS-CoV-2, 6-Gingerol was reported to exhibit potent anti-viral activity against chikungunya virus (CHIKV) infection of human hepatocyte HepG2 cells (Hayati et al., 2021) and human respiratory syncytial virus (HRSV) in respiratory upper and lower tract cell lines, HEp-2 and A549, respectively (Chang et al., 2013;Rathinavel et al., 2020;Chandra Manivannan et al., 2022). Eugenol was found to bind SARS-CoV-2 S1 protein to inhibit the host-pathogen interaction between human ACE 2 receptor and viral S protein (Paidi et al., 2021). ...
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The herbo-mineral formulation, Divya-Swasari-Vati (DSV), is a well-known Ayurvedic medication for respiratory ailments. In a recent pre-clinical study, DSV rescued humanized zebrafish from SARS-CoV-2 S-protein-induced pathologies. This merited for an independent evaluation of DSV as a SARS-CoV-2 entry inhibitor in the human host cell and its effectiveness in ameliorating associated cytokine production. The ELISA-based protein-protein interaction study showed that DSV inhibited the interactions of recombinant human ACE 2 with three different variants of S proteins, namely, Smut 1 (the first reported variant), Smut 2 (W436R variant) and Smut 3 (D614G variant). Entry of recombinant vesicular stomatitis SARS-CoV-2 (VSVppSARS-2S) pseudovirus, having firefly luciferase and EGFP reporters, was assessed through luciferase assay and fluorescent microscopy. DSV exhibited dose-dependent inhibition of VSVppSARS-2S pseudovirus entry into human lung epithelial A549 cells and also suppressed elevated levels of secreted pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) induced by viral infection mimicking Poly I:C-, S-protein- and VSVppSARS-2S pseudovirus. In human immune cells, DSV also moderated TNF-α-mediated NF-κB induction, in a dose-dependent manner. The observed anti-viral effect of DSV against SARS-CoV-2 is attributable to the presence of different metabolites Summarily, the observations from this study biochemically demonstrated that DSV interfered with the interaction between SARS-CoV-2 S-protein and human ACE 2 receptor which consequently, inhibited viral entry into the host cells and concomitant induction of inflammatory response.
... A broad research is being performed to obtain a potent formulation against coronavirus from herbal origin. The preclinical study on different herbal origins such as Zingiber officinale, Scutellaria baicalensis Georgi, Salvia miltiorrhiza Bunge, Allium sativum, Lecas aspera, Abutilon indicum, Sphaeranthus indicus Indigofera tinctoria, Vitex trifolia, Cassia alata, etc showed significant effectiveness for the management of SARS-CoV infection (Rathinavel et al., 2020;Choudhary et al., 2021). It has also been observed that sinigrin, β-sitosterol, aloe emodin, hahesperetin and indigo obtained from Isatis indigotica inhibited the SARS-CoV 3CLpro (Lin et al., 2005;Wen et al., 2007;Fuzimoto and Isidoro, 2020) observed that lignoids and abietane type diterpenoids have best anti-viral effects out of 221 phytocontituentsevaluated after isolating from Juniperus formosana, Chamaecyparis obtuse and Cryptomeria japanicaand so from Gentia scabra and Cassia toraas antiSARS-CoV potentiality (Wen et al., 2007;Natalie, et al., 2021). ...
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Objectives : The present study is focused to introduce a better preventive and treatment prospective to fight against the COVID-19 crisis by improving the immune system along with inhibiting the viral activity by a comprehensive review and supportive in-silico study. Methodology : The study was conducted with a systemic review on the phytochemicals possessing immunostimulatory potentiality, which was further supported by an in-silico investigation of thosephytocomponents in improving the immunity of the patient as well as in preventive measures which cancontribute a major part to manage the dangerous consequences of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). Results : In in-silico study showed that scutellarein, hesperidin andbaicalin exhibited strong binding affinity with ACE2, PAK1, Protease by strong molecular interaction forming several hydrogen bonds. Conclusion : The present finding interprets scutellarein, hesperidin and baicalin to be potential herbal immune boosters with antiviral potentiality which are to be further explored by in-vitro and in-vivo methods.
... Gingerol formed hydrogenbonded interaction with those viral proteins but with different amino acid residues. There was also a hydrophobic interaction between them (74). The electronic distribution (DFT study) also provided a clear picture of SARS CoV-2 protein-gingerol interactions and supported the molecular docking results. ...
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Along with health concerns, interest in plants as food and bioactive phytochemical sources has been increased in the last few decades. Phytochemicals as secondary plant metabolites have been the subject of many studies in different fields. Breakthrough for research interest on this topic is re-juvenilized with rising relevance in this global pandemics' era. The recent COVID-19 pandemic attracted the attention of people to viral infections and molecular mechanisms behind these infections. Thus, the core of the present review is the interaction of plant phytochemicals with proteins as these interactions can affect the functions of co-existing proteins, especially focusing on microbial proteins. To the best of our knowledge, there is no work covering the protein-phenolic interactions based on their effects on microbiota and microbial infections. The present review collects and defines the recent data, representing the interactions of phenolic compounds-primarily flavonoids and phenolic acids-with various proteins and explores how these molecular-level interactions account for the human health directly and/or indirectly, such as increased antioxidant properties and antimicrobial capabilities. Furthermore, it provides an insight about the further biological activities of interacted protein-phenolic structure from an antiviral activity perspective. The research on the protein-phenolic interaction mechanisms is of great value for guiding how to take advantage of synergistic effects of proteins and polyphenolics for future medical and nutritive approaches and related technologies.
COVID-19 is a running story with an unexpected end. Despite the large effort to provide effective treatment and prophylaxis, many people are still getting infected. This may be explained by the continuous virus mutations, and hence, the attenuation of the vaccine’s efficacy. Therefore, long-life boosting of the body’s immunity is a hopeful way against SARS-CoV-2 infection. Medicinal plants and other complementary and alternative remedies were used effectively in treating numerous mankind’s health problems. Recently, a lot of studies have confirmed the effect of natural products, cupping therapy, and acupuncture against SARS-CoV-2. The aim of this chapter is to remind ourselves of the natural pharmacy that God gave us, by shedding the light on the importance of some herbs and traditional remedies in the management of SARS-CoV-2 infection.
Human corona viral infection leads to acute breathing disease and death if not diagnosed and treated properly in time. The disease can be treated with the help of simple natural compounds, which we use in day-to-day life. These natural compounds act against several diseases but their drug targeting mechanism needs to be improved for more efficient and promising applications. In the present study five compounds (gingerol, thymol, thymohydroquinone, cyclocurcumin, hydrazinocurcumin) from three Indian medicinal plants (ginger, black cumin, turmeric) and its hyaluronic acid (HA) conjugates were docked against initially deposited spike structural proteins (PDB ID 6WPT) and its mutant variant D-614G (PDB ID 6XS6). Docking study result reveals that all the HA conjugates showed the most effective inhibitor of S-protein of initially deposited and D-614G variant forms of SARS-CoV-2. The compounds like Gingerol, Thymol, Thymohydroquinone, Cyclocurcumin, Hydrazinocurcumin, Hydroxychloroquinone, and hyaluronic acid conjugates inhibit the viral protein of both wild-type and mutated S-protein of SARS-CoV-2. The molecular docking studies of phytocompounds with initial deposited and variant spike protein targets show superior binding affinity than with the commercial repurposed viral entry inhibitor hydroxychloroquine. Further, the docking result was modeled using MD simulation study shows excellent simulation trajectories between spike proteins and HA conjugates spices constituents than its free form. DFT analysis was carried out to affirm the reason behind the highest binding affinity of HA conjugates over its free form towards SARS-CoV-2 spike protein targets. Further HA conjugates synthesis and its evaluation against SARS-CoV-2 in vitro studies are needed to prove our novel idea for an anti-viral drug.
Polycystic ovary disorder (PCOD) is hormonal disorder among reproductive-age women. Causing enlarged ovaries with small cysts on the outer edges in patients with PCOD, the secretion rate and metabolism of androgens and estrogens are disrupted. The pathophysiology of the syndrome is complex and there is no single defect from which it is known to result, it is hypothesized that insulin resistance is a key factor. With regards to the increasing prevalence of PCOD and associated mental and physical problemsas well as the effects of changes in sex hormones in development of this disease, our aim is to investigate the effects of synthetic drug and herbal drug in the serum levels of sex hormones and ovarian tissue. Several Pharmacological studies have described the use of various Ayurvedic medicinal plants and their constituents play the important role for the treatment of PCOD.Therefore, this drug can be partly effective in this syndrome via affecting the different hormones and serum levels of ovarian morphology, weight and representing an opportunity to investigate and discovery new bioactive products. This review discussed some synthetic and herbal drug which has the potential for the treatment of PCOD.
In the present study, in silico PLpro inhibitory potential of 28 polyphenolic compounds was validated, which possesses in vivo inhibitory potential against different SARS-CoV-2 replication enzymes. Among 28 polyphenolic compounds amentoflavone, tiliroside, papyriflavanol A and indinavir exhibited good binding affinity of toward PLpro has been considered for further virtual screening processes. Comprehensive analysis indicates that amentoflavone, tiliroside, and papyriflavanol A phenolic compounds demonstrate very high stability and higher inhibiting potential to bind with the Thr158 and Leu162 dyad of PLpro among 28 phenolic compounds. Further ADME and DFT analysis of amentoflavone, and papyrifalvanol A reveal that possess excellent pharmacokinetic and molecular electrostatic potentials. MD simulation and MM-GBSA analysis of amentoflavone, tiliroside, and one anti-viral drug indinavir toward PLpro (PDB ID 6W9C) result revealed that phenolic compounds amentoflavone, tiliroside possess excellent simulation trajectories toward the binding pocket of PLpro essential to inhibit SARS-CoV-2 multiplication. Further MM-GBSA analysis affirm that PLpro-amentoflavone complex exhibit high MMGBSA score of −106.56Kcal/mol. However, further human clinical trials are essential to justify their clinical pertinence.
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The entire world is experiencing the Covid, a worldwide pandemic, which has caught the world'sregard for the immune system. As the world scrambles to find a solution for Covid-19, health specialists have recommendedsupporting the body's immunity. The immune system guard against microbes, infection,and different Microorganismsmight assist with limiting the impacts and hurry the recuperation from the illness. Coronavirus has a troublingly high death rate.An individual with a solid Immune system and great body health hasthe option to recuperate from respiratory syndrome coronavirus 2 (SARS-CoV-2) diseases with practically no inconveniences becausethe invulnerable framework created antibodies. Invulnerability will be "our friend in need" against the infection. The thought is that ifyou don't have an intense weapon to battle the adversary, a solid and compelling safeguard is simply the smartest choice to secure. Now also there are lots of people in the world whohavethe risk of getting containment with the COVID-19 Virus. Ginger plays a big role in increasing the defense system of the bodya potent immunomodulatory agent that can help thepopulationtoprevent thecovid-19infection.
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COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 Mpro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use.
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There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.
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In the present study, anti-diabetic phyto compounds of Ficus racemosa bark methanolic extract was screened through GCMS and evaluated its anti-diabetic potential in vitro and in silico (molecular docking and DFT analysis) approaches. The anti-diabetic phyto compounds β-Sitosterol, β-amyrin, betulinic acid and stigmasterol were explored through GCMS analysis. In vitro anti-diabetic α-amylase inhibitory effect of the plant (IC50 19.50 µg) was found equipotent when compared with standard acarbose drug (IC50 11.25 µg). In silico molecular docking study of Ficus racemosa phytocompounds and reference standard drug acarbose with four crucial targets of diabetes (GLP-1, GSK, GK & IRTK) revealed that phytocompound β-amyrin shows highest binding affinity with all four screened targets -6.9,-9.1,-8.9,-10.7 kcal/mol than standard drug acarbose -4.7, -8.1, -7.7 & -8.8 kcal/mol respectively. Further DFT analysis of top 3 ant-diabetic phytocompounds (β-amyrin, betulinic acid and stigmasterol) of F.raemosa and standard acarbose was done. It was found that β-amyrin possess more stability and biological activity as it shows less energy gap, low hardness, and more softness -0.06277eV, 0.031385eV and 31.86235eV than reference standard acarbose possess more energy gap, more hardness, and low softness -0.24436 eV, 0.12218 eV and 8.18464 eV respectively.
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Flavonoids are widely distributed as secondary metabolites produced by plants and play important roles in plant physiology, having a variety of potential biological benefits such as antioxidant, anti-inflammatory, anticancer, antibacterial, antifungal and antiviral activity. Different flavonoids have been investigated for their potential antiviral activities and several of them exhibited significant antiviral properties in in vitro and even in vivo studies. This review summarizes the evidence for antiviral activity of different flavonoids, highlighting, where investigated, the cellular and molecular mechanisms of action on viruses. We also present future perspectives on therapeutic applications of flavonoids against viral infections.
PubChem ( is a key chemical information resource for the biomedical research community. Substantial improvements were made in the past few years. New data content was added, including spectral information, scientific articles mentioning chemicals, and information for food and agricultural chemicals. PubChem released new web interfaces, such as PubChem Target View page, Sources page, Bioactivity dyad pages and Patent View page. PubChem also released a major update to PubChem Widgets and introduced a new programmatic access interface, called PUG-View. This paper describes these new developments in PubChem.
221 extracts from various parts of 33 Indian medicinal plants were tested to identify their protease inhibitor potential. The aqueous extract of Aporosa lindleyana, methanol and aqueous extracts of Baliospermum montanum, chloroform extract of Gymnema sylvestre, aqueous extract of Hedyotis corymbosa and aqueous extract of Plectranthus amboinicus showed significant inhibition of α-Chymotrypsin, Leucine Amino peptidase and Papain.The aqueous extracts of Plectranthus amboinicus exhibited significant inhibition of HIV -1 specific Protease. A biology guided fractionation methodology devised in this study pinpointed the flavonoid bioactive fraction PA-9 to exhibit inhibition of HIV-1 protease at 100μg/ml. © 2016, International Journal of Pharmacognosy and Phytochemical Research. All rights reserved.
Ethnopharmacological relevance: Ginger, Zingiber officinale Roscoe, is a common spice and also a widely used medicinal plant in ancient China. Ginger is an ingredient of Ge-Gen-Tang (Kakkon-to; GGT). GGT has been proved to have antiviral activity against human respiratory syncytial virus (HRSV). However, it is unknown whether ginger is effective against HRSV. Aim of the study: To find a readily available agent to manage HRSV infection, the authors tested the hypothesis that ginger can effectively decrease HRSV-induced plaque formation in respiratory mucosal cell lines. Materials and methods: Effect of hot water extracts of fresh and dried gingers on HRSV was tested by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Ability of ginger to stimulate anti-viral cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA). Results: Fresh ginger dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (p<0.0001). In contrast, dried ginger didn't show any dose-dependent inhibition. 300 μg/ml fresh ginger could decrease the plaque counts to 19.7% (A549) and 27.0% (HEp-2) of that of the control group. Fresh ginger was more effective when given before viral inoculation (p<0.0001), particularly on A549 cells. 300 μg/ml fresh ginger could decrease the plaque formation to 12.9% when given before viral inoculation. Fresh ginger dose-dependently inhibited viral attachment (p<0.0001) and internalization (p<0.0001). Fresh ginger of high concentration could stimulate mucosal cells to secrete IFN-β that possibly contributed to counteracting viral infection. Conclusions: Fresh, but not dried, ginger is effective against HRSV-induced plaque formation on airway epithelium by blocking viral attachment and internalization.
SMILES (Simplified Molecular Input Line Entry System) is a chemical notation system designed for modern chemical information processing. Based on principles of molecular graph theory, SMILES allows rigorous structure specification by use of a very small and natural grammar. The SMILES notation system is also well suited for high-speed machine processing. The resulting ease of usage by the chemist and machine compatability allow many highly efficient chemical computer applications to be designed including generation of a unique notation, constant-speed (zeroeth order) database retrieval, flexible substructure searching, and property prediction models.
Ginger is used in more ways than any other spice. This monograph, published in two parts, comprehensively reviews production, trade, processing, chemistry, and evaluation of quality. Botany, world varieties, agronomy, crop improvement and potential are reviewed briefly with emphasis on the yield of functional components. Processing for the market, international trade patterns, and factors influencing them are discussed. Derived products such as ginger powder, syruped ginger, volatile oil, and oleoresin are discussed in greater detail. The increasing world demand for quality products of added value such as the oleoresin and volatile oil show prospects for their production in the growing countries. The chemistry of the components which contribute aroma and pungency that characterize ginger is critically reviewed. The second part deals with evaluation of quality. The physico-chemical parameters prescribed as a measure of quality for ginger and its products in the existing standards can assure only hygienic quality and purity, and possibly the source, when new parameters such as GC-fingerprints are included. The importance of sensorily evaluating flavor quality is emphasized to understand the variation in flavor quality required by the industrial and retail markets. Related areas, such as problems in sensory evaluation of intense flavored substances, objective flavor profile analysis, and correlation of instrumental and sensory data, are discussed and our recent work in this area is summarized. Areas where more research are needed are indicated. Other areas briefly discussed are functional, physiological, and toxicological properties in use of ginger; biosynthetic aspects of the components stimulating flavor; and structure and pungency and chemistry of spices from allied species and genera. A comprehensive bibliography is provided to aid in further study and research.
The dried rhizomes of Indonesian ginger, Zingiber officinale, were investigated for antirhinoviral activity in the plaque reduction test. Fractionation by solvent extraction, solvent partition, and repeated chromatography guided by bioassay, allowed the isolation of several sesquiterpenes with antirhinoviral activity. The most active of these was beta-sesquiphellandrene [2] with an IC50 of 0.44 microM vs. rhinovirus IB in vitro.