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Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study

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The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from Nigella sativa L, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the Mpro protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of Nigella Sativa against coronavirus infection
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doi.org/10.26434/chemrxiv.12055716.v1
Identification of Compounds from Nigella Sativa as New Potential
Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking
Study.
Salim Bouchentouf, Noureddine Missoum
Submitted date: 31/03/2020 Posted date: 02/04/2020
Licence: CC BY-NC-ND 4.0
Citation information: Bouchentouf, Salim; Missoum, Noureddine (2020): Identification of Compounds from
Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study..
ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12055716.v1
The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires
use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new
probable inhibitors of COVID-19 by molecules from Nigella sativa L, which is highly reputed healing herb in
North African societies and both Islamic and Christian traditions. The discovery of the Mpro protease structure
in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the
main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa
and drugs under clinical test was performed using Molecular Operating Environment software (MOE).
Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to
the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by
hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active
site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given
by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir
(-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19
treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive
use of Nigella Sativa against coronavirus infection.
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1
Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019
Novel Coronasvirus (Covid-19): Molecular Docking Study.
Bouchentouf Salim1,2,* and Missoum Noureddine2,3
1: Facult of Technology, Doctor Tahar Moulay University of Saida, Algeria
*bouchentouf.salim@yahoo.fr , salim.bouchentouf@univ-saida.dz
2: Laboratory of Natural products and Bioactives, University of Tlemcen
3: Faculty of Technology, University Hassiba Ben Bouali of Chlef, Algeria
Abstract
The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation
requires use of all resources to remedy this scourge. In the present study, using molecular docking, we
identify new probable inhibitors of COVID-19 by molecules from Nigella sativa L, which is highly reputed
healing herb in North African societies and both Islamic and Christian traditions. The discovery of the Mpro
protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for
treatment. Focusing on the main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of
compounds from Nigella Sativa and drugs under clinical test was performed using Molecular Operating
Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -
6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and
better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471
kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802
kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-
5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have
the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of
identified and to encourage preventive use of Nigella Sativa against coronavirus infection.
Keywords: COVID-19, Nigella Sativa, 6LU7, 2GTB, molecular docking, MOE software.
Introduction
During December 2019 a novel coronavirus (COVID-19) has been reported from Hubei province in Chinai.
The virus associated with human to human transmission is causing several human infections and disorder
not only in the respiratory apparatus but also in the digestive tract and systemically ii iii iv. On March 11,
2020, world health organization characterizes COVID-19 as a pandemic which caused until 30, March, 2020
30,105 death and 638,146 confirmed cases over the worldv. Due to gravity of the situation, urgent and
complementary efforts from researchers are necessary to find therapeutic agents and new preventive
methods. Description of COVID-19 virus shown three important proteins know as papain-like protease
(PLpro), 3C-like protease (3CLpro) and spike protein to be attractive target for drug developmentvi. Viral
polypeptide onto functional proteins is processed by Coronavirus PLpro which is also a deubiquitinating
enzyme that can dampen host anti-viral response by hijacking the ubiquitin (Ub) systemvii viii. It has been
shown also that SARS-3CLpro is a cysteine protease indispensable to the viral life cycle ix . Angiotensin-
converting enzyme 2 (ACE2) is used by Coronavirus spike protein as a receptor to help the virus enter cells
x .The potential target (Mpro)/chymotrypsin-like protease (3CLpro) from COVID-19 (6LU7) have been
successfully crystallized by Liu et al (2020) and repositioned in Protein Data bank (PDB)xi. Medicinal
chemists are focusing also on the main protease of SARS-Coronavirus (2GTB) to develop antiviral
treatments of the virus causing COVID-19xii because it shares 96 % similarityxiii. Some in silico preliminary
studies have been conducted to find small molecules from herbal plants with the potential to inhibit 2019
novel coronavirus xiv xv xvi.
2
Contagious disease treatment and control is widely demonstrated by effectiveness of medicinal herbs xviixviii
xix xx xxi. Absence of specific therapy for COVID-19 leads population over many regions in the world to use
medicinal herbs knows in ethnophamacologie as antiviral. In our present study and inspired by recent
molecular docking studies xxii xxiii we illustrate interactions between small molecules from North African
medicinal herb; Nigella sativa L in order to identify the favorable molecules for COVID-19 treatment and
compare them to proposed drugs such as chloroquine hydroxychloroquine,azithromycin, arbidol, remdesivir,
and favipiravir xxiv xxv. The in silico study was done using Molecular Operating Environment software
(MOE)xxvi. The present study will provide other researchers with important investigation way to identify
new COVID-19 treatment and use of natural products.
Material and methods
Medicinal herb choice
Based on local survey we reported that Nigella sativa L. commonly known as black seed or black cumin
(Haba sawda) is widely recommended in society during the COVID-19 crisis for their probable antiviral
effects. The large traditional use of black cumin as panacea (universal healer) in North African societies
came from Islamic belief and also Bible xxvii. Nigella sativa is cited by many research papers for its multiple
benefits as antiviral, anti-inflammatory, anti-cancer, analgesicetc xxviii xxix xxx xxxi.
Preparation of both enzymes and ligands
Download of 3clpro/Mpro COVID-19 and 3clpro/Mpro SARS-coronavirus three dimensional structures were
done from Protein Data Bankxxxii under PDB ID 6LU7 and 2GTB respectivelyxxxiii xxxiv. Crystallographic
properties of 6LU7 and 2GTB are reported in table 1. Table 2 reports major chemical compounds of Nigella
sativa L collected from literature xxxv xxxvi xxxvii xxxviii xxxix xl. The 3-dimensional (3D) structures of main
chemical compounds from Nigella sativa were downloaded in .sdf format from PubChemxli. Lipinski’s
physicochemical parameters rule xlii xliii xliv were also studied for each ligand and reported in table 3.
Chemical structures of main drugs under clinical tests for treatment of COVID-19 are reported in table 4 xlv
xlvi xlvii.
Identification of the preferred region of the receptor that interacts with ligands is known by active site
prediction and isolation protocolxlviii. Using Hamiltonian AM1 (Austin model 1) implanted in MOE and field
strengths in the MMFF94x (Merck molecular force field) energy of the protein was minimized. In addition,
water molecules were removed from the protein surface so that the interaction region will not be hidden
while docking. By use of site-finder module implanted in MOE, active sites of 6LU7 and 2GTB were
identified and shown in figure 1 and 2 respectively. Also both natural ligands (compounds from Nigella
sativa L ) and proposed drugs were submitted to energy minimizing under default conditions of temperature
= 300°K and pH = 7.
Table 1: Crystallographic properties of enzymes
Enzyme
PDB
Code
Classification
Organism
Expression
system
Resolution
Total
structure
weight
(DA)
chaine
COVID-19
main
protease
6LU7
VIRAL
PROTEIN
Bat SARS-
like
coronavirus
Escherichia
coli
BL21(DE3)
2.1 Å
34506.34
A
SARS
coronavirus
main
peptidase
2GTB
HYDROLASE
SARS
coronavirus
CUHK-L2
Escherichia
coli
2 Å
34649.48
A
3
Table 2: Chemical structures of major compounds from Nigella Sativa.
Nigellicine
Nigellidine
Nigellimine
Carvacrol
α- Hederin
6- Thymol
Thymoquinone
Dithymoquinone
thymohydroquinone
Table 3: Expanded Lipinski’s physicochemical parameter for Nigella sativa compounds.
Ligands
Molecular
weight
(g/mol)
Toxicity
Retro
synthese
%
Hdonn
Hacc
Log
P
Log
S
TPSA
2)
1
Nigellicine
246.27
no
33.33
1
3
1.06
-2.19
60.85
2
Nigellidine
294.35
no
100
1
2
2.94
-3.7
43.78
3
Nigellimine
203.24
no
100
0
3
2.56
-2.42
31.35
4
Carvacrol
150.22
no
100
1
1
2.82
-2.69
20.23
5
α- Hederin
750.97
no
35.85
7
12
3.52
-8.24
195.60
6
Thymol
150.22
no
100
1
3
2.82
-2.69
20.23
7
Thymoquinone
164.20
no
100
0
2
1.67
-2.48
34.14
8
Dithymoquinone
328.41
no
0.00
0
4
2.71
-3.90
68.28
9
thymohydroquinone
166.22
no
100
2
2
2.53
-2.01
40.46
4
Table 4: Chemical structures of main proposed drugs for COVID-19 treatment
ligands
Name
Structures
Pub Chem CID
Expanded Lipinski’s rule
1
Chloroquine
2719
Properties
Value
MW(g/mol)
320.89
H-donor
2
H-acceptor
1
LogP
3.39
LogS
-3.76
TPSA (Å)
29.36
2
Hydroxychloroquine
3652
Properties
Value
MW(g/mol)
336.89
H-donor
3
H-acceptor
2
LogP
2.37
LogS
-3.23
TPSA (Å)
49.59
3
Azythromycine
447043
Properties
Value
MW(g/mol)
751.01
H-donor
7
H-acceptor
11
LogP
-0.93
LogS
-3.64
TPSA (Å)
182.48
4
Arbidol
131411
Properties
Value
MW(g/mol)
477.42
H-donor
1
H-acceptor
3
LogP
6.07
LogS
-5.82
TPSA (Å)
54.70
5
Remdesivir
121304016
Properties
Value
MW(g/mol)
602.58
H-donor
4
H-acceptor
10
LogP
1.24
LogS
-5.17
TPSA (Å)
203.01
6
Favipiravir
492405
Properties
Value
MW(g/mol)
157.10
H-donor
2
H-acceptor
3
LogP
-1.19
LogS
-1.33
TPSA (Å)
84.55
5
Figure 1: Isolated active site of 6LU7 in complex with an inhibitor N3 (PRD_002214)
Figure 2: Isolated active site of SARS coronavirus main peptidase (PDB 2GTB) inhibited by an aza-peptide
epoxide
Docking and Building Complexes
Docking using Dock module implanted in MOE, consists of positioning ligands into active site of 6LU7 and
2GTB with most of default tools to predict how molecules interacts with the binding site of the receptor xlix l
li . First docked molecules series were proposed drugs and respective reference inhibitors (PRD_002214 of
6LU7 and AZP for 2GTB) in order to compare obtained score with score from chosen ligands of Nigella
sativa L. Table 5 gives obtained scores by drugs under clinical test and inhibitor ligands (PRD_002214 and
AZP). Table 6 shows scores of second docked ligand series from compounds from Nigella Sativa.
Table 5: Obtained docking score by drugs under clinical test and inhibitors.
ligand
molecules
Score (Kcal/mol)
Reference
ligand
6LU7
2GTB
PRD_002214
-10.4669304
/
AZP
/
-7.49913883
1
Chloroquine
-6.2930522
-6.20844936
2
Hydroxychloroquine
-5.57386112
-5.51465893
3
Azythromycine
-5.57062292
-6.25860453
4
Arbidol
-7.15007734
-6.74997902
5
Remdesivir
-6.35291243
-7.07897234
6
Favipiravir
-4.23310471
-4.12183571
6
Table 6: Obtained score from docking of Nigella Sativa compounds with 6LU7 and 2GTB
Ligand
Score (kcal/mol)
6LU7
2GTB
Nigellicine
-5.11696768
-5.05794954
Nigellidine
-6.29734373
-5.58170891
Nigellimine
-4.80306292
-5.07316256
Carvacrol
-4.8290143
-4.45325089
α- Hederin
-5.25583553
-6.50204802
Thymol
-4.50417519
-4.03594398
Thymoquinone
-4.71068573
-4.41701126
Dithymoquinone
-4.45150137
-4.99905396
thymohydroquinone
-4.22977924
-4.23156166
Results and discussion
Obtained results showed that Nigellidine gives the lowest energy (-6.29734373 Kcal/mol) in complex with
6LU7, which is the best score when compared to other docked compounds. Nigellidine gives score close to
the one given by chloroquine (-6.2930522 Kcal/mol) and better score than hydroxychloroquine (-
5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Nigellidine in complex with 6LU7 (Figure
3A and 3B) shows two hydrogen possible interactions with amino acid MET49 (H-donor) with a distance
about 4.25Å and energy of -0.7Kcal/mol and π-H interaction with amino acid THR190 with a distance about
4.24Å and energy of -1.3Kcal/mol. Interactions between the rest of compounds from Nigella sativa and
6LU7 are reported in table 7.
Figure 3A: 2D diagram interaction between
Nigellidine and 6LU7
Figure 3B: 3D diagram interaction between
Nigellidine and 6LU7
Docking results with 2GTB show that α- Hederin gives better score (-6.50204802 kcal/mol) than
chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-
4.12183571kcal/mol). Alpha-hedrin in complex with 2GTB (figure 4A and 4B) show that only one
hydrogen interaction (H-acceptor) with amino acid Gly 143 is possible with distance about 2.92 Å and
energy of -2.2 Kcal/mol.. Interactions between the rest of compounds from Nigella sativa and 2GTB are
reported in table 9.
Figure 4A: 2D diagram interaction between α-
hederin and 2GTB
Figure 4A: 3D diagram interaction between α-
hederin and 2GTB
7
Table 7: Interactions and 2D diagrams of compounds from Nigella Sativa with 6LU7
Ligand
Structure interactions
Type of interactions
Nigellicine
Two hydrogen interaction are possible
with:
- Amino acid THR 190 (H-donor) with
distance about 3.11 Å and energy of -3.3
Kcal/mol.
- Amino acid GLU 166 (π-H) with
distance about 4.12 Å and energy of -1.0
Kcal/mol
Nigellimine
No perceptible interactions, only
electrostatics exist (Van der Waals)
Carvacrol
Three hydrogen interactions are possible
with:
- Amino acid HIS 41 (H-π) with
distance about 4.35 Å and energy of -0.6
Kcal/mol.
- Amino acid GLN 189 (π-H) with
distance about 4.16 Å and energy of -0.8
Kcal/mol.
- Amino acid THR 190 (π-H) distance
about 4.67 Å and energy of -0.8
Kcal/mol
α- Hederin
Three hydrogen interaction are possible
with:
- Amino acid HIS 164(H-donor) with
distance about 2.83 Å and energy of -1.8
Kcal/mol.
-Amino acid CYS 145 with distance
about 4.08 Å and energy of -1.1
Kcal/mol.
- Amino acid MET 165 distance about
3.73 Å and energy of -0.6 Kcal/mol
8
Thymol
Only one hydrogen interaction (π-H) is
possible with amino acid GLN189 with
distance about 4.24 Å and energy of -0.7
Kcal/mol.
Thymoquinone
Only one hydrogen interaction (π-H) is
possible with amino acid THR 190 with
distance about 4.70 Å and energy of -0.8
Kcal/mol.
Dithymoquinone
Only one hydrogen interaction (H-
acceptor) is possible with amino acid
THR 190 with distance about 2.89 Å and
energy of -3.9 Kcal/mol.
Thymohydroquinone
Only one hydrogen interaction (π-H) is
possible with amino acid GLU 166 with
distance about 4.46 Å and energy of -1.0
Kcal/mol.
9
Table 8: Interactions and 2D diagrams of compounds from Nigella sativa with 2GTB
Ligand
Structure interactions
Type of interactions
Nigellicine
Three hydrogen interaction are
possible with:
- Amino acid CYS 145 (H-donor)
with distance about 3.91 Å and
energy of -0.7 Kcal/mol.
- Amino acid GLY 143 (H-acceptor)
with distance about 3.04 Å and
energy of -2.2 Kcal/mol.
- amino acid CYS 145 (H-acceptor)
distance about 3.51 Å and energy of
-1.4 Kcal/mol
Nigellidine
Only one hydrogen interaction (H-
acceptor) is possible with amino
acid HIS 163 with distance about
3.01 Å and energy of -11.6
Kcal/mol.
Nigellimine
Only one hydrogen interaction -π)
is possible with amino acid HIS 41
with distance about 3.95 Å.
Carvacrol
There are non-perceptible
interactions, only electrostatics (Van
der Waals) interactions are
perceptible.
10
Thymol
There are non-perceptible
interactions, only electrostatics (Van
der Waals) interactions are
perceptible.
Thymoquinone
There are non-perceptible
interactions, only electrostatics (Van
der Waals) interactions are
perceptible.
Dithymoquinone
There are non-perceptible
interactions, only electrostatics (Van
der Waals) interactions are
perceptible.
Thymohydroquinone
Only one hydrogen interaction (H-
acceptor) is possible with amino
acid GLY143 with distance about
3.20 Å and energy of -0.7 Kcal/mol.
Conclusion
The aim of the present study is to identify molecules from natural products which may inhibit COVID-19 by
acting on the main protease (Mpro). Obtained results by molecular docking showed that Nigellidine and α-
hederin are main compounds from Nigella sativa which may inhibit COVID-19 giving the same or better
energy score compared to drugs under clinical tests. Those results encourage further in vitro and in vivo
investigations and also encourage traditional use of Nigella sativa preventively.
11
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... Among the group of plant prevention agents during the coronavirus pandemic, we can also cite Nigella sativa L.'s (Black cumin) bioactive constituents that have been noticed as promising inhibitors of COVID-19 in molecular docking work [50]. ...
... IC 50 inhibition averages of measured protease activities are: 3 µM (CAG), 5 µM (ECG), 6 µM (GCG), 7 µM (EGCG) and 75 µM PB 2 . The other compounds do not show any inhibitory activities. ...
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Citation: Brahmi, F.; Vejux, A.; Ghzaiel, I.; Ksila, M.; Zarrouk, A.; Ghrairi, T.; Essadek, S.; Mandard, S.; Leoni, V.; Poli, G.; et al. Role of Diet and Nutrients in SARS-CoV-2
... Among the group of plant prevention agents during the coronavirus pandemic, we can also cite Nigella sativa L.'s (Black cumin) bioactive constituents that have been noticed as promising inhibitors of COVID-19 in molecular docking work [50]. ...
... IC 50 inhibition averages of measured protease activities are: 3 µM (CAG), 5 µM (ECG), 6 µM (GCG), 7 µM (EGCG) and 75 µM PB 2 . The other compounds do not show any inhibitory activities. ...
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Coronavirus illness (COVID-19) is an infectious pathology generated by intense severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This infectious disease has emerged in 2019. The COVID-19-associated pandemic has considerably affected the way of life and the economy in the world. It is consequently crucial to find solutions allowing remedying or alleviating the effects of this infectious disease. Natural products have been in perpetual application from immemorial time given that they are attested to be efficient towards several illnesses without major side effects. Various studies have shown that plant extracts or purified molecules have a promising inhibiting impact towards coronavirus. In addition, it is substantial to understand the characteristics, susceptibility and impact of diet on patients infected with COVID-19. In this review, we recapitulate the influence of extracts or pure molecules from medicinal plants on COVID-19. We approach the possibilities of plant treatment/co-treatment and feeding applied to COVID-19. We also show coronavirus susceptibility and complications associated with nutrient deficiencies and then discuss the major food groups efficient on COVID-19 pathogenesis. Then, we covered emerging technologies using plant-based SARS-CoV-2 vaccine. We conclude by giving nutrient and plants curative therapy recommendations which are of potential interest in the COVID-19 infection and could pave the way for pharmacological treatments or co-treatments of COVID-19.
... Recently, silico-based modeling studies demonstrated that the docked complex between thymoquinone (TQ) and the E protein of SARS-CoV-2 presented immersive interactions indicating the potential inhibitory effects of N.Sativa natural chemical compounds (78). According to another in cillico study, nigelledine (an alkaloid component) docked with 6LU7 (SARS-CoV-2 protease) active sites and showed an energy complex score better than those of favipiravir and hydroxychloroquine (79). Moreover, alpha-Hederin (a saponin component of N. Sativa), which docked with 2GTB (SARS coronavirus peptidase) active sites showed an energy score better than those of favipiravir, hydroxychloroquine, and chlorquine (79,80). ...
... According to another in cillico study, nigelledine (an alkaloid component) docked with 6LU7 (SARS-CoV-2 protease) active sites and showed an energy complex score better than those of favipiravir and hydroxychloroquine (79). Moreover, alpha-Hederin (a saponin component of N. Sativa), which docked with 2GTB (SARS coronavirus peptidase) active sites showed an energy score better than those of favipiravir, hydroxychloroquine, and chlorquine (79,80). ...
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Background: SARS-CoV-2 is the causative agent of the novel coronavirus disease (COVID-19). This virus is responsible for the pandemic which has resulted in the current global health crisis. Remdesivir is now used as an FDA-approved medication in addition to some emergency use authorization (EUA) agents such as Actemra (Tocilizumab), Sotrovimab, and REGEN-COV (Casirivimab and Imdevimab) to contain the COVID-19 infection. However, they are not 100% effective in all cases, and there are several hundreds of daily deaths worldwide. Furthermore, since nearly one year as of the beginning of global vaccination, various vaccines have been evaluated not completely efficient in containing new variants of SARS-CoV-2, although they have significantly reduced mortality. Herbal medicines with evidence-based beneficial effects can have positive roles in immunity enhancement, prevention of infection, and antiviral effects. This review presents the updates of some herbal medicines that may have potential effects on the containment of the COVID-19, especially those with antitussive, antipyretic, anti-viral, anti-inflammatory, and antioxidant effects. Methods: In this narrative review, a thorough literature review was conducted on the entries of Google Scholar, PubMed, Web of Science (Clarivate Analytics), Scopus and, and Science Direct published since 2019. This study includes the recently published papers, randomized clinical trials (RCTs), and World Health Organization updates about the COVID-19. The inclusion criteria were the papers that described the effects of the most efficient types of herbal medicines on the containment of the COVID-19. Results: Analyzing nearly more than 40 medicinal plants, we found seven herbals (Myrtus communis, Zingiber officinale, Allium Sativum, Nigella Sativa, Glycyrrhiza glabra, and Thymus Vulgaris) that might have some positive effects on deferent stages of the COVID-19. Conclusion: Since some herbal medicines might help alleviate or relieve the symptoms of the COVID-19 or have other therapeutic effects, randomized controlled trials should be conducted to confirm these effects.
... Salim and Noureddine performed molecular docking for reference inhibitor AZP (PubChem Code: 5287723) against SARS coronavirus main peptidase and determined -7.499 kcal/mol as binding constant that is higher than the that of 1-3. They also analyzed the interactions for some well-known antiviral drugs such as remdesivir (-7.079 kcal/mol), favipiravir (-4.122 kcal/mol) and hydroxychloroquine (-5.515 kcal/mol) [43]. We also docked favipiravir, hydroxychloroquine, nelfinavir, remdesivir, and lopinavir into SARS coronavirus main peptidase with our protocol. ...
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... Arterial hypertension disease in sub-Saharan Africa is a problem of immense medical and economic significance because of its high prevalence in urban areas, its late or incomplete detection, the economic problems associated with its treatment, and the consequences of its complications [4]. According to research, a quarter of adults from half of African countries may have high blood pressure in their lifetime [5]. During 2019 year, the Algerian Ministry of Health announced that 23.6% of the population is suffering from high blood pressure disease, which represents more than 8 million people affected, while 71.9% of them don't receive treatment [6]. ...
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Blood pressure disorder causes serious diseases in the cardiovascular system such as arterial hypertension. According to the World Health Organization, an estimated 1.13 billion people worldwide have hypertension, and most of them (two-thirds) live in low- and middle-income countries. It is poorly controlled and constitutes one of the leading causes of premature death. In Africa, nearly 40% of adults in many countries have high blood pressure, but most wouldn't even know it. In 2019, Algeria announced that 24% of the population suffers from the arterial hypertension and around 72% of those who were tested positive had not received treatment. Among the processes related to hypertension, the angiotensin converting enzyme I (ACE) plays an important role in the regulation of the blood pressure. The talk about the high potential of the hawthorn and rosemary plants to treat hypertension was so spread in the Algerian culture, which prompted to study the molecules of these plants and descript they behavior with the angiotensin-converting enzyme by calculating energy affinity. Using molecular docking approach, identification and evaluation of the inhibitory potential of ACE by selected herbs was attempted. In addition, and in order to identify the most suitable molecules which can be developed to oral drugs considering their adsorption, distribution, metabolism, and excretion (ADME), Lipinski’s rules were applied using free SwissADME tool. Our study provides clearer insight interaction properties of known putative inhibitors of ACE such as Caffeic acid, Quercetin, Luteolin, Eugenol, Rosmaquinone, and Rosmaquinone β, which may be developed into drugs after in-vitro and in-vivo tests and also encourage use of medicinal herbs for treatment of arterial hypertension.
... Components of the plant can bind to viral fusion proteins inhibiting viral entry to the host cells, they also can decrease expression of ACE2 [80]. A molecular docking study showed that nigellidine and α-hederin from Nigella Sativa have better energy scores toward 6LU7 and 2GTB, which are the main proteases found in CoVs, active sites rather than HCQ, CQ, and favipiravir [81]. ...
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Objectives Due to the rapid spread of COVID-19 worldwide, many countries have designed clinical trials to find efficient treatments. We aimed to critically report the characteristics of all the registered and published randomized clinical trials (RCTs) conducted on COVID-19, and summarize the evaluation of potential therapies developed in various regions.Evidence acquisitionWe comprehensively searched PubMed, Cochrane Library, Web of Science, Scopus, and Clinicaltrial.gov databases to retrieve all the relevant studies up to July 19, 2021, in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. We included all English-language published/registered RCTs on COVID-19, and excluded non-RCT, in-vitro/in-vivo, editorials, and review studies. Two reviewers independently evaluated all the records, and then analyzed by using SPSS 17.ResultsWithin 3018 included studies, 2801 (92.8%) and 217 (7.2%) were registered or published RCTs consisting of about 600 synthetic drugs. Herbal medicines have been studied in 23 trials (10.6%) among the published RCTs and in 357 registered RCTs (12.7%). Hydroxychloroquine 23 (10.6%) and convalescent plasma 194 (6.9%) alone or in combination with other agents were the most frequently used interventions in published and registered RCTs, respectively. Most published RCTs have been conducted in Western Pacific Region (WPRO) (50 trials, 23.0%) including 45 trials from China. Also, a greater proportion of registered RCTs have been conducted in the Region of the Americas (PAHO) (885 trials, 31.6%) including 596 RCTs from the United States (U.S). Globally, 283 registered trials have been conducted to assess new developed vaccines for COVID or previously established for other disorders.Conclusion The present study highlighted the wide range of potential therapeutic agents in published and registered COVID-19 clinical trials across a wide range of regions. However, it is urgently required to global coordination in order to conduct more well-designed trials and progress in discovering safe and effective treatments.Graphical abstract
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Ag(I), Pt(IV), and Au(III) metal complexes of novel ligand 2-[2'-(6-methoxybenzothiazolyl)azo]-3-methyl-4-nitro phenol (6-MBTAMN) have been synthesized and characterized by ¹H NMR, ¹³C NMR, FT-IR, UV-Vis, Mass spectra, CHNS, atomic absorption spectrophotometry, molar conductance and magnetic susceptibility. Results confirmed that the ligand coordinates the metal ion to form a mononuclear complex via (N, N, O) atoms of the azomethine group, azo group, and phenolic group, respectively. Tetrahedral geometry is suggested for Ag(I)-Complex, an octahedral geometry is proposed for Pt(IV)-Complex, and a square planar geometry is suggested for Au(III)-Complex. The density functional theory (DFT) was used to calculate significant parameters for ligand and metal complexes, including optimization energy, HOMO, and LUMO. Newly synthesized azo compounds have also been demonstrated to have antimicrobial properties against bacteria and fungi. The complexes are more effective against bacteria than standard antimicrobials (Novobiocin and Cycloheximide), but less effective against fungi. Based on in silico molecular docking, the study demonstrated that the azo fused compounds interact critically with the androgen receptor prostate cancer mutant H874Y ligand binding domain bound with testosterone and an AR 20-30 peptide (ART) using the Molecular Operating Environment module (MOE). Further, the antioxidant activity of novel azo compounds was evaluated using DPPH radical scavenging, which demonstrated that Ag (I) metal complex possess potent antioxidant properties. The cytotoxic abilities of selected compounds by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays against PC3 (human prostate adenocarcinoma) and HUVECs (normal human umbilical vein endothelial cells).
Chapter
The coronavirus disease 2019 (COVID-19) was identified as the cause of an outbreak of respiratory illness in Wuhan in 2019. Some of the antivirals presently being tried are known anti-HIV (combination of lopinavir and ritonavir) and the rejected anti-ebola virus (remdesivir) drugs. Others are chloroquine, hydroxychloroquine and azithromycin. Till date, there is no specific antiviral treatment that has proven effective in the management of the pandemic. The infected victims primarily rely on symptomatic treatments and supportive care. This COVID-19 outbreak has triggered researchers worldwide to embark on more high-quality researches, in addition to the preventive measures, to manage the public health emergency in both the short- and long-term. Membrane lipids like cholesterol, glycerophospholipids and sphingolipids play key role in modification of intracellular membrane structures for virus replication. This chapter discussed the roles of membrane lipids in coronavirus replication, and inhibition of lipids biosynthesis for possible management of coronavirus disease.
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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 1.7.4.5 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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Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as “Public Health Emergency of International Concern” on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.
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Background: The aim of these studies was to assess the potential of the Rif (northern Morocco) with regard to medicinal and aromatic plants used in the treatment of respiratory system diseases. Methods: The ethnobotanical and ethnopharmacological studies were conducted in the Rif region for two campaigns (June 30th, 2016 to June 1st, 2018). In total, 674 local traditional healers were interviewed. Information was collected using open-ended and semi-structured interviews, analyzed and compared by quantitative ethnobotanical indices such as family importance value (FIV), the relative frequency of citation (RFC), plant part value (PPV), fidelity level (FL) and informant consensus factor (ICF) were used to analyze the obtained data. Results: The study identified a total of 41 medicinal plant species belonging to 22 botanical families. The most important family is that of the Lamiaceae represented by 8 species. Concerning the diseases treated, Asthma have the highest ICF (0.97), the leaf was considered the most used part of the plant (PPV=0.482) and the majority of the remedies were prepared in the form of decoction. Conclusions: The results of these present studies showed the existence of indigenous ethnomedicinal knowledge of medicinal and aromatic plants in the the Rif to treat respiratory system diseases. Further research on phytochemical and pharmacological should be considered to discover new drugs from these documented plants.
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Kourosh Hasanzadeh Ghahramanloo,1 Behnam Kamalidehghan,2 Hamid Akbari Javar,3 Riyanto Teguh Widodo,1 Keivan Majidzadeh,4 Mohamed Ibrahim Noordin1 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Medical Genetics Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), 3Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), 4Breast Cancer Research Center (BCRC) Academic Center for Education, Culture and Research, Tehran, Iran Abstract: The objective of this study was to compare the oil extraction yield and essential oil composition of Indian and Iranian Nigella sativa L. extracted by using Supercritical Fluid Extraction (SFE) and solvent extraction methods. In this study, a gas chromatography equipped with a mass spectrophotometer detector was employed for qualitative analysis of the essential oil composition of Indian and Iranian N. sativa L. The results indicated that the main fatty acid composition identified in the essential oils extracted by using SFE and solvent extraction were linoleic acid (22.4%–61.85%) and oleic acid (1.64%–18.97%). Thymoquinone (0.72%–21.03%) was found to be the major volatile compound in the extracted N. sativa oil. It was observed that the oil extraction efficiency obtained from SFE was significantly (P<0.05) higher than that achieved by the solvent extraction technique. The present study showed that SFE can be used as a more efficient technique for extraction of N. Sativa L. essential oil, which is composed of higher linoleic acid and thymoquinone contents compared to the essential oil obtained by the solvent extraction technique. Keywords: Nigella sativa L., essential oil extraction, supercritical fluid extraction, solvent extraction, fatty acid composition, thymoquinone, linoleic acid
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Objective: To identify, present and review the respiratoty medicinal plants which used by Urmian herbalists. Methods: The list of traditional healers of West Azarbaijan Province was prepared and data were obtained by direct observation, interviews and the questionnaires After that, herbarium samples were collected from the desired area and deposited in herbarium unit of the Faculty of Agriculture, Urmia University, Urmia, Iran. Results: Our results demonstrated that 20 medicinal plants from 10 plant families are used to treat respiratory disorders. Also, the most plant part that used for treating of respiratory disorders was seed (27%) and the most traditional form prescribed by herbalists was boiled (54%). Forty three percentage of Urmia herbalists have used herbs for the treatment of cough. Conclusions: People in this area have a strong belief that plants have a positive impact in the treatment of respiratory disorders and they have used medicinal plants since ancient times to treat these disorders. Our study revealed the importance of herbal medicines and traditional medicine in this area as medicinal resource for drug discovery in future.
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Background: A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. Methods: Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. Results: Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat_SARS-like coronavirus sequences. Specifically, in the 5'-part spanning the first 11,498 nucleotides and the last 3'-part spanning 24,341-30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat_SARS-like coronavirus sequences, whereas in the middle region spanning the 3'-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. Conclusions: The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.