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Virtual screening of COVID-19 drug from three Indian traditional medicinal

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Research Journal of Biotechnology
Review Paper:
Virtual screening of COVID-19 drug from three Indian
traditional medicinal plants through in silico approach
Thirumalaisamy Rathinavel1, Selvankumar Thangaswamy2, Subramanian Ammashi3 and Suresh Kumarasamy4*
1. Department of Biotechnology, Sona College of Arts and Science, Salem (Dt.) 636 005, Tamil Nadu, INDIA
2. Department of Biotechnology, Mahendra Arts and Science College (Autonomous), Namakkal (Dt) 637 501, Tamil Nadu, INDIA
3. Department of Biochemistry, Rajah Serfoji Government College (Autonomous), Thanjavur (Dt.) 613 005, Tamil Nadu, INDIA
4. Department of Biotechnology, MGR College, Hosur, Krishnagiri (Dt) 635 130, Tamil Nadu, INDIA
*sureshbioteck@yahoo.com
Abstract
Novel Corona Virus (2019 nCoV/COVID-19) emerged
from Wuhan city of Hubei Province China in November
2019. Now it causes pandemic disease COVID-19
across the globe in 2020. There is no proper
medication and vaccine treatment option available for
novel corona virus. There is a global urge set to
prepare effective drug and vaccines from various
possible routes against SARS-CoV-2. In the present
study, four ligand groups (I - IV) were made
comprising of one commercial anti-viral drug group
(14 Nos) and three ligands group (84 Nos) constituted
from phytocompounds of three anti-viral Indian
Traditional Medicinal plants (ITMP) such as
Azadirachta indica, Phyllanthus niruri andrographis
paniculata to search effective drug candidate for
treating novel coronavirus. Four levels of in silico
virtual screening procedures (molecular docking,
Lipinski rule, ADME, DFT analysis) were employed to
sort out and choose potential drug candidate for
COVID-19.
Virtual screening of 98 ligands from four ligands group
was done against six corona viral protein targets
(SARS-CoV-1 and 2) through in silico approach.
Preliminary molecular docking analysis revealed that
twenty high scored ligands against viral target proteins
were subject to Lipinski rule of drug likeliness
screening. Based on Lipinski rule and some
consideration of best docking score, eight ligands were
chosen out of twenty ligands. Eight ligands chosen
from Lipinski rule were subjected to final in silico
virtual screening steps such as ADME and DFT
analysis. Finally in silico virtual screening analysis
showed four best ligands Baloxavir marboxil
(CID124081896), Limocinin (CID 14845550),
Formononetin 7 O Glucuronide (CID 71316927) and
Bisandrographolide A (CID12000062). One from each
ligands group was considered as best drug candidate
for SARS CoV-2.
Keywords: Andrographis paniculata, Azadirachta indica,
Corona Virus, COVID-19, SARS-CoV-1, SARS-CoV-2,
Phyllanthus niruri.
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Vol. 15 (10) October (2020)
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Introduction
Corona virus is derived from Greek word “korone’’ means
crown shape which refers to the characteristic appearance of
virus particle with spike protein in their enveloped surface.
Corona viruses are group of viruses causing diseases in birds
and mammals including human. Corona virus is divided into
four main types they are alpha, beta, gamma and delta
belonging to the family of Coronaviridae. Human corona
viruses cause infection in respiratory tract which ranges from
mild common cold like rhino virus to lethal severe acute
respiratory syndrome like SAR, MERS and COVID-19
belonging to the Beta Corona virus. Basically, Corona
viruses possess positive sense single stranded RNA as a
genetic material with bound nucleocapsid, which is further
enveloped by glycoprotein. The genome size of corona
viruses ranges from 26 to 32 KB in size.32
In 2019 December, several mysterious pneumonic cases
were reported in Wuhan city of China. Later it was identified
and related to Corona virus family named as SARS-CoV-2
or 2019 novel Corona virus. WHO officially named the
SARS-CoV-2 viral disease as COVID-19. Phylogenetic
analysis of SARS-CoV-2 is a new type of beta corona virus
family and it closely resembles Bat SARS corona virus (96%
similarity) than the SARS-CoV (79.5% similarity)32,35 which
indicate it may originate from bat. So far there are no
antiviral drugs and vaccine identified for SARS-CoV-2. It
infect humans through its spike (S) protein with human
ACE2 receptor.
Sequence similarity and binding domain analysis of SARS-
CoV and SARS-COV-2 reveal that SARS-CoV-2 has strong
binding affinity towards ACE2 with similar spike protein
receptor binding domain. Hence the epitope of two corona
viruses drug and antibodies targeting will provide insight
into the novel drug identification in future. 3,8,34,27
Most of the people in developing countries rely upon
complementary and alternative medicinal practices to treat
various diseases, even though a complementary medicine
has modest proof towards their safety and effectiveness.
People have more faith on evidence-based research in
traditional medicine system and it gains larger acceptance of
peoples in the countries like India.7,16,18 Azadirachta indica
is a Indian Traditional Medicinal plant belonging to the
family of Meliaceae. Azadirachta indica plant parts (leaves,
bark, flower and fruit) are used traditionally for treating
many illness and disease from ancient times itself in India.
Research Journal of Biotechnology
Now in the modern world also, its usage is unavoidable in
several disease conditions such as
hypoglycemic, hypolipidemic, hepatoprotective,
hypotensive, cancer, skin diseases, , digestive disorders and
AIDS.
Azadirachta indica shows its anti-viral efficiency in treating
small pox and chicken pox. 25 It claims its usage to cure
COVID-19 with unsupported scientific evidence. Several
active ingredients of Azadirachta indica include
azadirachtin, nimbin and nimbidine, zadirachtin,
diterpenoids, triterpenoids, polyphenolic compounds.2
Phyllanthus niruri is an Indian traditional medicinal plant
belonging to the family of phyllanthaceace comprising of
about 700 plants.15 It is used as a ingredient in more than
hundreds of ayurvedic formulations utilized to treat various
diseases. Extracts of Phyllanthus niruri plant is used in the
treatment of HIV-AIDS, Jaundice and Hepatitis B Virus. It
possesses anti-viral, anti-inflammatory, hypotensive and
hypoglycemic effects. It inhibits Hepaptitis B viral DNA
polymerase, 29 HIV viral replication26 anti-plasmodial
activity, analgesic activity.10,19,23
Andrographis paniculata is a plant belonging to the family
of Acanthaceae. Recently its herbal preparations were used
by several countries due to its wide range of
pharmacological effects including anti-cancer, anti-
hepatitis, anti-HIV, anti-malarial, cardiovascular,
hepatoprotective and immunostimulatory effects.
Andrographis paniculata possess significant anti-viral
properties against dengue virus, human papilloma virus,
Herpes simplex virus, influenza A virus, HIV. 1,
Phytocompounds of Andrographis paniculata possess
significant anti-viral activity without causing any cytotoxic
effects to humans. Remarkably andrographolide phyto
compounds from Andrographis paniculata possess anti-viral
properties against Chikungunya viral infection11 and also act
as potential inhibitor against COVID-19 viral protein
targets.9
In our present study, the solution for global problem
COVID-19 is searched from phytocompounds of three
important anti-viral Indian traditional medicinal plants
(ITMP) such as Azadirachta indica, Phyllanthus niruri and
Andrographis paniculata through in silico virtual screening
approaches.
Ligand Generation: Four different group of ligands (Group
I – IV) have been framed to choose potential anti-viral
ligands from total ligands of four ITMP without missing
potential drug candidate for Corona viral target proteins,
they are group–I ligand comprising 14 number Commercial
Antiviral drugs, group–II ligand comprising of 33
phytocompounds of Phyllanthus niruri, category– III ligand
comprising of 30 phytocompounds of Azadirachta indica
phytocompounds, category– IV ligands comprising of 21
phytocompounds of Andrographis paniculata (Table 1). 2D
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Vol. 15 (10) October (2020)
Res. J. Biotech
structures of phytocompounds from Azadirachta indica,
Phyllanthus niruri andrographis paniculata and commercial
anti-viral drugs have been retrieved from Pubchem, a
database of chemical molecules. Retrieved 2D SDF file
format was submitted to Online SMILES convertor and
Structure file generator31 and converted into standard 3D
PDB format for further in silico virtual screening analysis.
Viral Target Protein: 3D crystal structures of Spike
proteins, Main Protease and Nucleocapsid Protein Targets of
each Corona viruses SARS-CoV-1 - 5WRG, 1UK3, 2CJR/
SARS-CoV-2 - 6LZG, 7BUY, 6M3M respectively were
retrieved from Research Collaboratory of Structural
Bioinformatics - Protein Data Bank (www.rcsb.org) using
their PDB ID.3
Molecular Docking: Totally six viral targets protein from
two corona virus SARS-CoV and SARS-CoV-2 and 98
ligands (14 Antiviral drugs and 84 phytocompound from
three Indian traditional plants) were taken for our study. Grid
map for docking of protein binding pocket was calculated
using Autogrid. The grid size for x, y and z points of
dimension was set for each viral target protein as follows;
5WRG - 98x96x136, 1UK3 - 60x80x77, 2CJR - 95x67x93,
6LZG - 62x71x111, 7BUY- 50x66x59, 6M3M -87x66x71.
Autogrid was used to set the grid points space (0.375 Å) for
all the viral protein targets. Other parameters of docking
such as docking assessment (~ 10 times), population size
(150), energy evaluation (maximum number 250,000)
generations (maximum number 27,000), rate of mutations
(0.02), rate of cross-over (0.8) and other parameters of
docking were set with default values using the autotor utility
of the auto dock tool.
Drug Likeliness and ADME Calculations: Drug likeliness
parameters of phytocompounds were done using Swiss
ADME online server. Drug likeliness of the
phytocompounds was examined based on violations of
Lipinski rule of five. Further the screened ligands possessing
higher docking score with more than 3 viral targets having
one Lipinski rule violations and ligands with zero violations
were also taken to next levels of in silico screening.
PreADMET web based application is used to determine
Pharmacokinetic properties of ligands with high docking
score (at least 3 viral targets with 1 violation of Lipinski) and
the ligands with zero violation of Lipinski. PreADMET
predicts the various pharmacokinetic parameters associated
with ADME behaviour of phytocompounds.
DFT Analysis: The determination of molecular electrostatic
potential (MEP) indicates the electrophilic and nucleophilic
reactive sites of the compounds and the energy gap between
highest occupied molecular orbital (HOMO) and lowest
unoccupied molecular orbital (LUMO) providing high and
low electron density regions on the compounds performed
through Density functional theory (DFT) calculations. The
DFT calculations were performed for phytocompounds and
commercial antiviral drugs done using functional B3LYP
Research Journal of Biotechnology
with 6-3IG** basic set in Gaussian 09. The important
parameter, HOMO-LUMO orbital energies that are used to
assess the ionization energy, electron affinity,
electronegativity, electronic chemical potential, molecular
hardness, softness and electrophilicity index are calculated
to reveal the compounds stability and chemical reactivity.
Molecular Docking Analysis
Docking results of three targets of SARS CoV-1 with
phytocompounds of three Indian medicinal plant shows
good binding affinity and docking score ranging from -5.6
to -10.7 kcal/mol than commercial anti-viral drugs -5.8 to -
11.4 kcal/mol. Docking results of three targets from SARS
CoV-2 with phytocompounds show better binding affinity -
5.2 to -10.4 kcal/mol than commercial ant-viral drugs
binding score 5.2 to -10.8 kcal/mol (Table 2A to 2D).
Similar results were reported.17,26
Top two docking scores from each ligands group with each
viral target protein target are considered for next level of
anti-viral drug screening. Four ligands (CID 67286591, CID
124081896, CID 92727, CID 121304016) were chosen from
group–I possessing highest docking score among category I
ligands. Especially Pimodivir (CID 67286591) exhibits
highest binding affinity and docking score of -9.2, -10.4, -
5WRG-Pimodivir (CID 67286591) Docking Pose & Interaction Plot (-
9.2Kcal/mol)
5WRG- Theaflavin-3-Gallate (CID 136825044) Docking Pose & Interaction
Plot(-11.0Kcal/Mol)
Figure 1 a and b: Docking Pose and Interaction plot for 5WRG against Pimodivir and Theaflavin-3-Gallate
126
Vol. 15 (10) October (2020)
Res. J. Biotech
8.7, -10.4 kcal/mol against 5WRG, 2CJR, 7BUY and 6M3M
respectively by forming (3,3),(1,2), (2,4),(0,10) alkyl
interactions and hydrogen bonding of compound with viral
targets. Similarly Baloxavir marboxil (CID 124081896)
from Group I ligands exhibits second top docking score and
highest binding affinity of -9.2, -9.7, -9.0, -9.3 kcal/mol
against viral protein targets 5WRG, 2CJR, 6LZG and 6M3M
respectively (Table 3) (Figure 1-2).
Six ligands from group II form top two docking score with
the six viral target proteins. Notably compound
Formononetin 7 O Glucuronide (CID 71316927) forms
highest binding affinity score of -10.8, -10.1, -10.3 kcal/mol
against 2CJR, 6LZG and 6M3M. Similarly, Theaflavin 3
Gallate (CID 136825044) forms best binding score -11.0, -
10.1, -10.6, -8.9 with 5WRG,2CJR, 6LZG and 7BUY. Five
compounds from group III form top two docking score
molecules among them. In that Lupeol (CID 259846) and
Caryophyllin (CID 10494) form best docking score and
binding affinity with viral protein target. Five compounds
from group IV hold top two docking score position among
them. Notably Bisandrographolide A (CID 12000062)
andrographolactone (CID 44206466) and 3-O-beta-D-
glucopyranosyl 14,19-dideoxyandrographolide (CID
11576609) form best docking score molecules among them
(Table 4) (Figure 3-6).
Research Journal of Biotechnology Vol. 15 (10) October (2020)
Res. J. Biotech

1UK3- Lopinavir (CID 92727) Docking Pose & Interaction Plot(-10.7Kcal/mol)

1UK3- Procyanidin dimer (CID 122738) Docking Pose & Interaction Plot(-
11.4Kcal/mol)
Figure 2 a and b: Docking Pose and Interaction plot for 1UK3
against Lopinavir and Procyanidin dimer

2CJR-Pimodivir (CID 67286591) Docking Pose & Interaction

Plot(-10.4Kcal/mol)

2CJR- Formononetin 7 O Glucuronide (CID 71316927) Docking

Pose & Interaction Plot(-10.8Kcal/mol)

Figure 3 a and b: Docking Pose and Interaction plot for 2CJR against Pimodivir and
Formononetin 7 O Glucuronide

127
Research Journal of Biotechnology Vol. 15 (10) October (2020)
Res. J. Biotech

6LZG- Baloxavir marboxil (CID 124081896) Docking Pose & Interaction Plot(-9.0Kcal/mol)

6LZG- Theaflavin 3 Gallate (CID 136825044) Docking Pose & Interaction Plot (-
10.6Kcal/mol)

Figure 4 a and b: Docking Pose and Interaction plot for 6LZG against Baloxavir marboxil and Theaflavin 3 Gallate

7BUY- Pimodivir (CID 67286591) Docking Pose & Interaction Plot (-8.7Kcal/mol)

7BUY- Bisandrographolide A (CID 12000062) Docking Pose & Interaction Plot (-

9.3Kcal/mol)

Figure 5 a and b: Docking Pose and Interaction plot for 7BUY against Pimodivir and Bisandrographolide A

128
 Research Journal of Biotechnology Vol. 15 (10) October (2020)
Res. J. Biotech
Table 1
List of Four Ligands Groups comprising One Commercial Anti-Viral Drugs Group and Three Indian Traditional
Medicinal Plants (ITMP) Groups
Pub Chem ID Compound Pub Chem ID Compound Pub Chem ID Compound Pub Chem ID Compound
Group I - Commercial Anti- Group II - Phyllanthus niruri Group III - Azadirachta indica Group IV - Andrographis paniculata
Viral Drugss Phytocompounds Phytocompounds Phytocompounds
CID_2130 Amantadine CID_358901 Phyllanthin CID_5280794 Stigmasterol CID_11624161 14-Deoxyandrographolide
CID_5071 Rimantadine CID_182140 Hypophyllanthin CID_11230 Terpinen-4-ol CID_9848024 Neoandrographolide
CID_60855 Zanamivir CID_128861 Cyanidin CID_7461 Gamma CID_5318517 Andrographolide
terpinene
CID_65028 Oseltamivir CID_443650 Delphidin 3 O CID_7463 4-Cymene CID_44593583 Andrographiside
glucoside
CID_154234 Peramivir CID_44256978 Malvidin 3 CID_94162 Sugiol CID_101563018 Isoandrographolide
Diglucoside
CID_502272 Laninamivir CID_122738 Procyanidin dimer CID_12308714 Azadiradione CID_5708351 14-Deoxy 11,12-
didehydroandrographolide
CID_492405 Favipiravir CID_1794427 Chlorogenic acid CID_5281303 Azadirachtin CID_11666871 Andrograpanin
CID_67286591 Pimodivir CID_6508 Quinic acid CID_259846 Lupeol CID_91884987 14-Deoxy-11-
hydroxyandrographolide
CID_124081896 Baloxavir CID_5281672 Myricetin CID_12004512 Gedunin CID_38350572 14-Deoxy-12-
marboxil hydroxyandrographolide
CID_131411 Umifenovir CID_5280343 Quercetin CID_12310088 Genistein 7 CID_11576609 3-O-beta-D-
Glucoside glucopyranosyl 14,19-
dideoxyandrographolide
CID_92727 Lopinavir CID_5281613 Diosmin CID_72276 Epicatechin CID_44206466 Andrographolactone
CID_392622 Ritonavir CID_5280445 Luteolin CID_10160231 Limocinone CID_44575263 8,17-Epoxy-14-
9 deoxyandrographolide
CID_37542 Ribavirin CID_932 Naringenin CID_10160232 Limocin A CID_12000062 Bisandrographolide A
0
CID-121304016 Remdesivir CID_442428 Naringin CID_14845550 Limocinin CID_5280443 Apigenin
CID_68071 Pinocembrin CID_14845542 Limocinol CID_188316 7-O-methylwogonin
CID_71316927 Formononetin 7 O CID_108058 Nimbin CID_12041831 Onysilin
Glucuronide
CID_5281811 Tectorigenin CID_100017 Nimbolide CID_13963762 Andrographidine A
CID_44258841 Kaempferol-3- CID_11119228 Nimbiol CID_ 5318484 Andrographidine C
Rutinoside
CID_4788 Phloretin CID_178770 Nimocinol CID_5280445 Luteolin
CID_136825044 Theaflavin 3 CID_73356511 Nimonol CID_5281653 1,8-Dihydroxy-3,7-
Gallate dimethoxyxanthone
CID_65373 Secoisolariciresinol CID_10095318 Nimbothalin CID_5281780 3,4-Dicaffeoylquinic acid
9
CID_332427 Lariciresinol CID_184937 Nimolicinol
CID_4133 Methyl salicylate CID_6442484 Nimbilin
CID_72 3,5 – Dihydroxy CID_180429 Nimolinin
Benzoic acid
CID_338 Salicylic acid CID_91747196 Cubebene
CID_689043 Caffeic acid CID_12303902 Copaene
CID_5317238 Ethyl Caffeate CID_6432312 Gamma
Elemene
CID_637542 p-Coumaric acid CID_5281520 Humulene
CID_129720117 p-Coumaroyl CID_9859094 Beta Elemene
glycolic acid
CID_10385447 8-5 Diferulic acid CID_10494 Caryophyllin
CID_5281855 Ellagic acid
CID_10151874 Valoneic acid
dilactone
CID_92158 Lupenone

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Res. J. Biotech
Table 2.1
Docking score of four Ligand group Compounds against Corona Viral (SARS CoV-1 and 2) Target Proteins
S.N. Ligand Compound SARS CoV-1 Viral Target Proteins SARS CoV-2 Viral Target Proteins
Group No
5WRG 1UK3 2CJR 6LZG 7BUY 6M3M
1. 2130 -6.0 -5.6 -6.2 -5.8 -5.2 -5.5
2. 5071 -7.2 -6.0 -6.4 -5.9 -5.7 -6.4
3. I 60855 -7.1 -7.6 -6.5 -6.4 -6.0 -7.9
4. 65028 -6.4 -6.3 -6.3 -6.6 -5.7 -6.6
5. 154234 -6.2 -6.8 -6.7 -6.6 -6.3 -6.3
6. 502272 -6.6 -7.5 -6.6 -6.6 -5.6 -7.2
7. 492405 -6.1 -6.0 -6.0 -5.6 -5.0 -5.9
8. 67286591 -9.2 -9.7 -10.4 -8.4 -8.7 -10.4
9. 124081896 -9.2 -9.8 -9.7 -9.0 -8.0 -9.3
10. 131411 -6.0 -7.3 -6.6 -6.7 -5.9 -6.2
11. 92727 -9.0 -10.7 -9.2 -8.0 -7.5 -9.1
12. 392622 -8.4 -10.0 -7.4 -8.0 -7.1 -8.0
13. 37542 -7.5 -6.9 -7.1 -7.1 -5.9 -7.1
14. 121304016 -8.4 -10.2 -8.4 -8.7 -8.4 -9.1
Table 2.2
Docking score of four Ligand group Compounds against Corona Viral (SARS CoV-1 and 2) Target Proteins
S.N. Ligand Compound SARS CoV-1 Viral Target Proteins SARS CoV-2 Viral Target Proteins
Group No
5WRG 1UK3 2CJR 6LZG 7BUY 6M3M
1. 358901 -6.8 -7.0 -6.9 -6.3 -6.2 -7.4
2. 182140 -8.3 -8.1 -6.6 -6.4 -5.8 -7.0
3. 128861 -9.1 -8.6 -8.7 -7.6 -7.5 -8.0
4. 443650 -8.6 -9.8 -8.1 -7.6 -7.8 -8.4
5. 44256978 -8.2 -10.2 -8.6 -7.7 -6.9 -8.2
6. 122738 -8.6 -11.4 -8.8 -9.2 -8.7 -9.6
7. II 1794427 -7.7 -8.9 -6.5 -8.5 -7.3 -8.0
8. 6508 -6.5 -6.1 -6.3 -5.9 -5.5 -5.6
9. 5281672 -9.3 -8.9 -8.9 -8.4 -7.3 -8.6
10. 5280343 -8.0 -8.9 -9.1 -9.7 -7.3 -8.8
11. 5281613 -10.3 -10.6 -10.1 -9.5 -8.8 -9.7
12. 5280445 -9.2 -8.6 -9.1 -9.8 -7.9 -8.8
13. 932 -7.8 -8.3 -8.8 -9.0 -7.7 -8.5
14. 442428 -9.5 -10.5 -9.3 -9.0 -8.5 -8.9
15. 68071 -8.6 -8.0 -9.0 -9.1 -7.6 -8.6
16. 71316927 -9.1 -9.4 -10.8 -10.1 -8.3 -10.3
17. 5281811 -8.0 -8.7 -9.0 -7.2 -6.9 -8.4
18. 44258841 -10.1 -11.0 -10.0 -9.7 -8.0 -9.9
19. 4788 -8.1 -8.3 -8.1 -8.2 -6.9 -7.8
20. 136825044 -11.0 -10.7 -10.1 -10.6 -8.9 -9.5
21. 65373 -7.4 -7.3 -8.1 -7.1 -5.7 -8.1
22. 332427 -7.7 -7.6 -9.0 -7.6 -7.7 -8.5
23. 4133 -5.7 -5.8 -6.0 -6.4 -5.4 -5.4
24. 72 -6.3 -6.2 -5.8 -6.3 -5.5 -5.6
25. 338 -6.2 -5.8 -6.2 -6.2 -5.3 -5.5
26. 689043 -6.8 -6.6 -6.5 -7.3 -5.9 -6.5
27. 5317238 -6.7 -6.7 -7.2 -7.6 -6.0 -6.4
28. 637542 -6.6 -6.7 -6.6 -7.1 -5.7 -6.0
29. 129720117 -7.1 -7.0 -7.5 -6.6 -6.0 -7.0
30. 10385447 -6.9 -8.0 -8.7 -7.7 -6.7 -8.7
31. 5281855 -8.3 -8.4 -9.1 -8.9 -7.5 -9.4
32. 10151874 -9.0 -10.3 -8.6 -9.4 -8.0 -10.1
33. 92158 -9.7 -9.5 -9.3 -9.6 -8.1 -10.5

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Table 2.3
Docking score of four Ligand group Compounds against Corona Viral (SARS CoV-1 and 2) Target Proteins
S.N. Ligand Compound SARS CoV-1 Viral Target SARS CoV-2 Viral Target
Group No Proteins Proteins
5WRG 1UK3 2CJR 6LZG 7BUY 6M3M
1. 5280794 -9.5 -9.2 -7.5 -8.1 -8.2 -10.2
2. 11230 -6.5 -6.2 -6.0 -5.5 -5.2 -5.6
3. 7461 -6.5 -6.0 -6.1 -6.9 -5.2 -5.4
4. 7463 -6.4 -6.1 -6.2 -7.0 -5.2 -5.4
5. III 94162 -8.5 -8.5 -8.5 -8.3 -7.9 -9.2
6. 12308714 -8.4 -10.3 -8.0 -8.7 -7.5 -9.0
7. 5281303 -7.7 -7.6 -8.0 -8.2 -7.0 -8.6
8. 259846 -9.6 -9.9 -8.2 -9.3 -8.4 -10.8
9. 12004512 -8.8 -9.6 -8.3 -8.7 -7.8 -9.7
10. 12310088 -9.3 -9.6 -10.3 -9.8 -7.9 -9.8
11. 72276 -9.0 -8.3 -8.5 -8.0 -7.5 -8.6
12. 101602319 -9.3 -9.1 -10.1 -8.8 -8.7 -9.7
13. 101602320 -9.0 -9.0 -8.0 -8.0 -7.6 -8.9
14. 14845550 -8.8 -10.7 -8.4 -9.0 -8.4 -9.1
15. 14845542 -9.1 -9.1 -9.3 -8.9 -8.2 -9.3
16. 108058 -6.8 -8.8 -7.5 -7.5 -7.2 -7.7
17. 100017 -9.3 -9.4 -7.7 -7.8 -7.4 -8.2
18. 11119228 -8.4 -7.9 -8.4 -8.0 -7.4 -8.5
19. 178770 -8.7 -8.8 -7.7 -8.0 -7.0 -8.9
20. 73356511 -8.6 -10.1 -7.6 -7.8 -7.1 -9.0
21. 100953189 -8.8 -8.1 -8.0 -8.3 -7.2 -8.7
22. 184937 -8.3 -10.0 -8.3 -8.9 -7.8 -8.4
23. 6442484 -8.3 -8.4 -8.4 -8.9 -7.9 -8.8
24. 180429 -8.5 -8.2 -7.8 -7.5 -8.0 -8.1
25. 91747196 -8.8 -6.8 -7.6 -6.8 -6.6 -7.0
26. 12303902 -7.0 -6.5 -7.5 -6.3 -5.9 -7.1
27. 6432312 -6.6 -6.3 -7.9 -6.3 -5.8 -6.6
28. 5281520 -7.6 -7.2 -7.4 -6.3 -6.0 -6.9
29. 9859094 -6.8 -6.3 -7.6 -5.9 -5.7 -6.5
30. 10494 -10.1 -11.0 -9.2 -9.4 -8.3 -10.7
Table 2.4
Docking score of four Ligand group Compounds against Corona Viral (SARS CoV-1 and 2) Target Proteins
S.N. Ligand Compound SARS CoV-1 Viral Target Proteins SARS CoV-2 Viral Target Proteins
Group No 5WRG 1UK3 2CJR 6LZG 7BUY 6M3M
1. 11624161 -8.0 -7.9 -8.8 -7.3 -7.6 -8.4
2. 9848024 -8.7 -8.9 -8.0 -8.6 -8.9 -9.4
3. 5318517 -8.4 -8.2 -7.9 -7.2 -7.6 -9.0
4. 44593583 -8.9 -9.5 -9.2 -8.3 -8.4 -9.3
5. 101563018 -9.3 -8.5 -8.0 -8.3 -7.3 -9.3
6. IV 5708351 -7.9 -7.9 -9.2 -7.9 -7.7 -8.5
7. 11666871 -8.7 -7.8 -8.5 -7.7 -7.7 -8.3
8. 91884987 -7.9 -7.8 -8.8 -7.5 -7.5 -8.7
9. 38350572 -9.2 -7.8 -8.8 -7.8 -7.7 -9.0
10. 11576609 -8.6 -9.1 -9.4 -8.1 -7.6 -9.8
11. 44206466 -8.7 -8.6 -9.8 -10.2 -8.1 -8.8
12. 44575263 -7.6 -7.7 -7.5 -7.4 -7.3 -8.5
13. 12000062 -9.7 -10.8 -8.9 -9.6 -9.3 -10.3
14. 5280443 -8.1 -8.5 -8.9 -9.0 -7.6 -8.5
15. 188316 -8.0 -8.2 -8.7 -8.7 -7.1 -8.6
16. 12041831 -8.5 -8.3 -8.9 -8.3 -7.2 -8.4
17. 13963762 -8.6 -9.0 -8.1 -8.1 -7.8 -9.2
18. 5318484 -8.5 -9.1 -8.8 -7.6 -8.0 -9.0

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19. 5280445 -8.0 -8.6 -9.1 -8.2 -7.9 -8.8
20. 5281653 -7.9 -8.4 -9.0 -9.2 -6.6 -8.2
21. 5281780 -9.4 -10.3 -8.9 -9.0 -7.1 -8.9

Table 3
Selected List of Compounds from four Ligand groups for Corona Virus (SARS CoV-1 and 2)
S.N. Ligand Compound Name Compound SARS CoV-1 Viral SARS CoV-2 Viral
Group No Target Proteins Target Proteins
5WRG 1UK3 2CJR 6LZG 7BUY 6M3M
1. Pimodivir 67286591 -9.2 -9.7 -10.4 -8.4 -8.7 -10.4
2. Baloxavir marboxil 124081896 -9.2 -9.8 -9.7 -9.0 -8.0 -9.3
3. I Lopinavir 92727 -9.0 -10.7 -9.2 -8.0 -7.5 -9.1
4. Remdesivir 121304016 -8.4 -10.2 -8.4 -8.7 -8.4 -9.1
5. Procyanidin dimer 122738 -8.6 -11.4 -8.8 -9.2 -8.7 -9.6
6. Diosmin 5281613 -10.3 -10.6 -10.1 -9.5 -8.8 -9.7
7. Formononetin 7 O 71316927 -9.1 -9.4 -10.8 -10.1 -8.3 -10.3
II Glucuronide
8. Kaempferol-3- Rutinoside 44258841 -10.1 -11.0 -10.0 -9.7 -8.0 -9.9
9. Theaflavin 3 Gallate 136825044 -11.0 -10.7 -10.1 -10.6 -8.9 -9.5
10. Lupenone 92158 -9.7 -9.5 -9.3 -9.6 -8.1 -10.5
11. Lupeol 259846 -9.6 -9.9 -8.2 -9.3 -8.4 -10.8
12. Genistein 7 Glucoside 12310088 -9.3 -9.6 -10.3 -9.8 -7.9 -9.8
13. III Limocinone 101602319 -9.3 -9.1 -10.1 -8.8 -8.7 -9.7
14. Limocinin 14845550 -8.8 -10.7 -8.4 -9.0 -8.4 -9.1
15. Caryophyllin 10494 -10.1 -11.0 -9.2 -9.4 -8.3 -10.7
16. Neoandrographolide 9848024 -8.7 -8.9 -8.0 -8.6 -8.9 -9.4
17. 3-O-beta-D glucopyranosyl 11576609 -8.6 -9.1 -9.4 -8.1 -7.6 -9.8
IV 14,19dideoxyandrographolide
18. Andrographolactone 44206466 -8.7 -8.6 -9.8 -10.2 -8.1 -8.8
19. Bisandrographolide A 12000062 -9.7 -10.8 -8.9 -9.6 -9.3 -10.3
20. 3,4-Dicaffeoylquinic acid 5281780 -9.4 -10.3 -8.9 -9.0 -7.1 -8.9
Legend – Top two docking scores in each ligand group against each viral target protein is in bold letter, which is considered for next
level of in silico screening (Drug likeliness calculation by Lipinski Rule)

Table 4
Top Two Docking Score Compounds from each Ligand groups with Corona Viral Target Proteins
(SARS CoV-1 and 2) and its interaction
S.N. Docking Docking No of No of Residues Involved in Alkyl Interactions and Hydrogen Bonding
Complex Score Alkyl H
(Target-Ligand) (-kcal/mol) Bonds Bonds
1. 5WRG-67286591 -9.2 3 3 Tyr738, Asp976*,Arg977#,Leu983,
2. 5WRG- -11.0 3 7 Asp296*,Ile299,Tyr300*,Thr302*,Val581,Gln599*, Ile652*,
136825044 Ser750*, Arg747*,Leu843
3. 5WRG-10494 -10.1 6 1 Ile299,Tyr300,Val581,Ser750*,Ala753,Ala754,Leu843
4. 5WRG-12000062 -9.7 7 3 Ile299,Gln599*,Pro651,Lys715*,Ala752,Ala754,Arg758*
5. 1UK3-92727 -10.7 4 5 Arg4#,Lys5#,Ala7,Gln127*, Trp207*, Glu288*
6. 1UK3-122738 -11.4 1 6 Lys5#,Gln127*,Arg131*,Lys137*,Trp207*,Glu288*
7. 1UK3-10494 -11.0 5 1 Arg4,Lys5*,Trp207,Ile286
8. 1UK3-12000062 -10.8 3 5 Arg4#,Lys5*,Ile286,Glu288*,Asp289*,
9. 2CJR-67286591 -10.4 1 2 Asn270*, Arg277*,Arg294
10. 2CJR-71316927 -10.8 3 5 Asn270*, Thr272*,Gly288*,Gln290*,Ile293,Arg294
11. 2CJR-12310088 -10.3 2 5 Asp270*,Thr272*,Arg277*,Gly288*,Ile293,Arg294,Ala360*
12. 2CJR-44206466 -9.8 5 1 Arg277,Ile293,Arg294,Asn270*
13. 6LZG-124081896 -9.0 1 1 Ala348*,Trp349

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14. 6LZG-136825044 -10.6 - 7 Ala99*,Tyr196*,Tyr202*,Trp203*,Asp509*,Ser511*,Arg514*
15. 6LZG-12310088 -9.8 2 4 Asn290*Ile291*,Pro415,Gln442*
16. 6LZG-44206466 -10.2 4 1 Met366,Pro415,Lys441*,His540,Lys541
17. 7BUY-67286591 -8.7 2 4 Pro108*,Gly109*,Val202,Asn203*,Thr292*,Phe294
18. 7BUY-136825044 -8.9 1 4 Gln110*,Thr111*,Asp153*,Pro293
19. 7BUY-101602319 -8.7 5 - Val202,His246,Ile249,Pro293,Phe294
20. 7BUY-12000062 -9.3 3 4 Phe8,Gly109*,Asp153*,Glu240*,His246,Pro293*,Phe294
21. 6M3M-67286591 -10.4 - 10 Gly70*,Val73*,Glu137*,Gln161*,Leu162*,Gln164*, Gly165*,
Thr166*,Tyr173*
22. 6M3M-92158 -10.5 2 1 Ile75,Leu162*,Pro163
23. 6M3M-259846 -10.8 3 - Trp53,Ile147,Ile158
24. 6M3M-12000062 -10.3 5 4 Ile75,Pro81,Glu137*,Leu162*,Pro163, Gly165*, Thr166*,
Leu168,Tyr173
Legend * symbol denotes amino acid residues with H bonding
Plain amino acid residues name and it position denotes alkyl interaction
# symbol denotes amino acid residues with both alkyl interactions and H bonding

6M3M-Pimodivir (CID 67286591) Docking Pose & Interaction Plot (-10.4Kcal/mol)

6M3M- Lupeol (CID 259846) Docking Pose & Interaction Plot (-10.8Kcal/mol)

Figure 6 a and b: Docking Pose and Interaction plot for 6M3M against Pimodivir and Lupeol

It was previously reported that docking of main protease of
SARS-CoV-2 virus is with three drugs namely, lopinavir,
darunavir and ritonavir whose binding scores are -
8.1Kcal/mol,-7.6Kcal/mol and -8.1Kcal/mol respectively.22
Numerous natural phytochemical compounds such as
quercetin, luteolin, hesperitin, emodin, curcumin, betulinic
acid, saiko saponin showed promising SARS-CoV-2 anti-
viral activity reported by Orhan et al.21
Potential inhibitor of Mpro such as remdesivir, lopinavir,
ritonavir has a docking score of -7.67, -7.33,-6.73Kcal/mol
respectively reported.4 In our present docking study selected
twenty compounds in preliminary screening showed very
good docking score in the range of -9.0 to -11.4 kcal/mol that
which proclaims that our study will bring better drug
candidate against corona viral protein targets with good
pharmacological profiles than any other proposed inhibitors
for corona virus.

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Drug Likeliness Prediction: Twenty ligands were chosen
(Table 5) based on preliminary docking analysis results,
these twenty ligands were subjected to next level of in silico
screening (i.e. Drug likeliness) using SWISS ADME online
server. Drug likeliness will avoid money and time
investment in the preclinical and clinical screening step of
drug discovery Lipinski rule of five was employed for look
over the drug likeliness parameters of twenty high scored
ligands against viral targets. Results of Drug likeliness
calculation based on Lipinski rule reveal that four ligands
(CID 67286591, CID 71316927, CID 9848024, CID
11576609) obey Lipinski rule with zero violation suitable for
next level of in silico screening four ligands (CID
124081896, CID 14845550, CID 10494 and CID 12000062)
with top docking score against two to five viral target having
one violation of Lipinski rule is also considered for next
level of in silico screening. Totally six ligands subjected to
ADME property calculations. Similar drug likeliness
prediction was done for phytocompounds to target against
corona viral protein molecular targets.12
ADME Calculations: ADME calculations of six selected
ligands were done through preADMET web based
application and their result was presented in Table 6.
Analysis of ADME components of eight selected ligands
exhibit very good Pharmacokinetic (absorption,
bioavailability and distribution) properties. All six selected
ligands possess good ADME property to act as better anti-
viral drug candidate. In absorption Part of ADME all eight
compounds showed good HIA in the range of 73-100%,
Caco2 permeability in the range of 7.81– 49.05nm/sec. In
Bioavailabilty part, tested compound shown Buffer and pure
water solubility in the range of 0.02 -699mg/l and 0.11 –
22.91mg/l respectively. In distribution part Compounds
possess very good plasma protein binding and Blood brain
Barrier Penetration values 71-100% and 0.01-7.87
respectively.
In that notably, Ligand Baloxavir marboxil (CID
124081896) shown highest HIA (100%) and Caco-2 cell
permeability (49.05 nm/sec) score. Ligand Limocinin (CID
14845550) shown highest skin permeability log Kp cm/hour
-0.91. Ligand 3-O-beta-D glucopyranosyl
14,19dideoxyandrographolide (CID11576609) possess
highest MDCK cell permeability score of 1.8009 nm/sec.
Ligand Caryophyllin (CID10494) exhibit very good buffer
solubility (699mg/L), Plasma protein binding (100%) and
BBB penetration (7.8792). Similar ADME calculation was
done for phytocompounds to target against corona viral
protein molecular targets.12
DFT Calculation: Analysis of DFT results of selected
ligands are shown in Table 7 and Figure.8 DFT helpful to
find out electron donor/electron acceptor characteristics of
phytocompounds and it became more valuable tool to assess
the various biological properties of phytocompound.
Localization of HOMO-LUMO orbital energy by DFT study
is gaining much importance in in silico docking to find out
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Res. J. Biotech
the reason behind the high molecular binding affinity of
compound with target proteins. In our DFT study anti-viral
drug Baloxavir marboxil (CID 124081896) and
Bisandrographolide A (CID 12000062) from Andrographis
paniculata shown more stability as they possess less energy
gap (i.e. less difference between Homo-Lumo orbital
energy) (-0.1272eV, -0.1536 eV), low hardness (0.0636 eV
and 0.0768) and more softness (15.7195eV and 13.0149 eV)
respectively when compared with other tested compounds.
Similarly, in Group II and Group III ligands such as
Formononetin 7 O Glucuronide (CID71316927) and
Limocinin (CID 14845550) shown less energy gap (-0.1704
and -0.1784eV) and good softness scores (11.729 and
11.2107eV) respectively. Hence our in silico virtual
screening study reveals that four compounds namely anti-
viral drug Baloxavir marboxil, Formononetin 7 O
Glucuronide from Phyllanthus niruri, Limocinin from
Azadirachta indica and Bisandrographolide from
Andrographis paniculata possess promising anti-viral
activity against SARS CoV-1 and 2 (Figure 7).
Similarly, our previous report phytocompound 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.28 Thus the in silico
screening of DFT calculations performed here is taking
better evidence for highest binding affinity of ligands and
highest docking score with SARS CoV-1 and 2 protein
targets.
Various drug manufacturing companies across the globe was
attempting to prepare drugs and vaccines against COVID-19
some of them listed below: Data obtained from COVID-19
drug and vaccine tracker (https://www.statnews.com/
feature/coronavirus/drugs-vaccines-tracker/) shown that
Chinese drug maker Ascletis Pharma is testing a
combination of antiviral drugs such as Danoprevir and
Ritonavir former one approved for hepatitis C and later one
approved for HIV is under clinical trial for COVID-19 in
Phase 4 stage.
Gilead Sciences testing drug, remdesivir, is an intravenous
treatment meant to block viruses from replicating SARS–
CoV-2 is in phase 3 clinical trials for COVID-19 drug. More
than dozens of companies are in different phases of clinical
trials to prepare drug and vaccines against COVID-19.
Anti-viral activity from natural origin against corona virus
was reported earlier by several authors. Saikosaponins are
naturally occurring triterpene glycosides compounds
isolated from Bupleurum sp., Heteromorpha sp. and
Scrophularia scorodonia. Medicinal plants exert antiviral
activity against HCoV-22E9.6 The extracts from Lycoris
radiata, Artemisia annua, Pyrrosia lingua and Lindera
aggregata have also been documented to display anti–
SARS-CoV and also eventually prevent early stages of
SARS-CoV-1 infections.14
 Research Journal of Biotechnology Vol. 15 (10) October (2020)
Res. J. Biotech
Table 5
Drug Likeliness Calculation by Lipinski Rule for Preliminary Selected Ligands for Corona Virus
(SARS CoV-1 and 2)
S.N. Ligand Compound Name Compound No Components Lipinski Rule of Lipinski
Group Five Rule
HBA HBD MW iLog P Violations
(10>) (5>) (500>) (5>)
1. Pimodivir 67286591 7 3 399.39 2.1 0
2. Baloxavir marboxil 124081896 9 0 571.55 3.68 1
I
3. Lopinavir 92727 5 4 628.8 3.44 1
4. Remdesivir 121304016 12 4 602.6 3.24 2
5. Procyanidin dimer 122738 12 10 578.52 2.05 3
6. Diosmin 5281613 15 8 608.54 3.05 3
7. Formononetin 7 O Glucuronide 71316927 10 4 444.39 2.48 0
8. Kaempferol-3- Rutinoside 44258841 21 12 770.64 2.21 3
9. II Theaflavin 3 Gallate 136825044 16 11 716.6 1.76 3
10. Lupenone 92158 1 0 424.7 4.54 1
11. Lupeol 259846 1 1 426.72 4.89 1
12. Genistein 7 Glucoside 12310088 10 6 432.38 2.11 1
13. Limocinone 101602319 1 0 424.7 4.92 1
14. III Limocinin 14845550 6 1 548.71 4.06 1
15. Caryophyllin 10494 3 2 456.7 3.92 1
16. Neoandrographolide 9848024 8 4 480.59 3.27 0
17. 3-O-beta-D glucopyranosyl 11576609
14,19dideoxyandrographolide 8 4 480.59 3 0
18. Andrographolactone 44206466 2 0 296.4 3.46 1
19. IV Bisandrographolide A 12000062 8 4 664.87 4.5 1
20. 3,4-Dicaffeoylquinic acid 5281780 12 7 516.45 1.25 3
Legend - Bolded Compounds are taken for next level of in silico virtual screening analysis (ADME and DFT)
Table 6
ADME Properties of final shortlisted ligands for Corona Virus (SARS CoV-1 and 2)
S.N. Pharmacokinetic Compounds ID
Properties 67286591 124081896 71316927 14845550 10494 9848024 11576609 12000062
1. Human Intestinal 90.06 100 73.24 96.58 95.99 78.92 79.55 91.83
Absorption (HIA
%)
Caco-2 Cell 19.28 49.05 7.81 30.52 21.88 18.12 17.72 20.87
Absorption

Permeability
(nm/sec)
MDCK Cell 0.0742 0.0631 0.3409 0.0436 0.0438 0.2300 1.8009 0.0434
Permeability
(nm/sec)
Skin Permeability -5.14 -4.33 -4.13 -0.91 -2.35 -4.18 -4.22 -1.33
(log Kp, cm/hour)
2. Buffer Solubility 283.70 39.62 76.36 423.66 699.01 34.78 10.0276 0.0240
Bioavail

(mg/l)
ability

Pure Water 0.1581 0.1852 22.91 0.11 0.0204 22.36 9.68 0.1417
Solubility (mg/l)
3. Plasma Protein 84.83 92.93 71.69 92.45 100 92.71 94.76 93.93
Distribution

Binding (%)
Blood Brain Barrier 0.1053 0.1375 0.0123 0.3407 7.8792 0.1404 0.1574 1.0260
Penetration

Legend - High scored compound for each ADME parameter is in bold letter

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Baloxavir Marboxil (Compound ID – CID 124081896)

Formononetin-7-O-Glucuronide (Compound ID – CID 71316927)

Limocinin (Compound ID – CID 14845550)

Bisandrographolide A (Compound ID – CID 12000062)

Figure 7: 2D and 3D structures of four Shortlisted Drug Candidate against Corona Virus (SARS CoV-1 and 2) from
in silico virtual screening

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a) Pimodivir Homo Orbital Energy b) Pimodivir Lumo Orbital Energy

c) Baloxavir Marboxil Homo Orbital d) Baloxavir Marboxil Lumo Orbital

Energy Energy

e) Formononetin 7 O Glucuronide f) Formononetin 7 O Glucuronide

Homo Orbital Energy Lumo Orbital Energy

g) Limocinin Homo Orbital Energy h) Limocinin Lumo Orbital Energy

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Res. J. Biotech

i) Caryophyllin Homo Orbital Energy j) Caryophyllin Lumo Orbital Energy

k) Neoandrographolide Homo Orbital Energy l) Neoandrographolide Lumo Orbital Energy

m) 3-O-beta-D-glucopyranosyl 14,19- n) 3-O-beta-D-glucopyranosyl 14,19-

dideoxyandrographolide Homo Orbital Energy dideoxyandrographolide Lumo Orbital Energy

o) Bisandrographolide A Homo Orbital Energy p) Bisandrographolide A Lumo Orbital Energy

Figure 8 (a-p): DFT study of Eight Shortlisted drug candidate against Corona Virus (SARS CoV-1 and 2)

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Table 7
DFT Calculation for shortlisted ligands form Virtual Screening for Corona Virus (SARS CoV-1 and 2)
Ligand Compound Name Compound HOMO LUMO Energy Ionization Electron Electro Electro Hardness Softness
Group No Gap potential affinity negativity chemical (𝜂) (𝜎)
(IE) (eV) (EA) (𝜒) potential (eV) (eV)
(eV) (eV) (𝜇) (eV)
Pimodivir 67286591 -0.2104 -0.0369 -0.1735 0.2104 0.0369 0.1236 -0.1236 0.0867 11.5267
I Baloxavir marboxil 124081896 -0.1897 -0.0624 -0.1272 0.1897 0.0624 0.1261 -0.1261 0.0636 15.7195
II Formononetin 7 O 71316927 -0.2135 -0.0430 -0.1704 0.2135 0.0430 0.1282 -0.1282 0.0852 11.7329
Glucuronide
Limocinin 14845550 -0.2198 -0.0414 -0.1784 0.2198 0.0414 0.1306 -0.1306 0.0892 11.2107
III Caryophyllin 10494 -0.2099 0.0249 -0.2348 0.2099 0.0249 0.0924 -0.0924 0.1174 8.5153
Neoandrographolide 9848024 -0.2332 -0.0345 -0.1987 0.2332 0.0345 0.1338 -0.1338 0.0993 10.0654
3-O-beta-D glucopyranosyl 11576609 -0.2305 -0.0360 -0.1944 0.2305 0.0360 0.1332 -0.1332 0.0972 10.2833
IV 14,19dideoxyandrographolide
Bisandrographolide A 12000062 -0.2168 -0.0631 -0.1536 0.2168 0.0631 0.1399 -0.1399 0.0768 13.0149
Legend –Chosen compound from each ligand group for drug candidate against Corona viral (SARS CoV-1 & 2) targets proteins is
in bold letter

It is reported that phenolic compounds such as myricetin,
scutellarein from Isatis indigotica and Torreya nucifera
found to inhibit SARS-CoV enzymes, such as the nsP13 are
helicase and 3CL protease.33 It reported that water extract
from Houttuynia cordata inhibits SARS-CoV 3CL protease
and RNA-dependent RNA polymerase activity.13 The
present study reveals that anti-viral compounds from ITMP
showed significant scores at each level of in silico screening.
Further clinical trials will need to reveal the biological
activity of selected ligand against corona viruses.
2. Alzohairy M.A., Therapeutics Role of Azadirachta indica
(Neem) and Their Active Constituents in Diseases Prevention and
Treatment, Evid Based Complement Alternat Med, 1-13 (2016)
3. Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N.,
Weissig H., Shindyalov I.N. and Bourne P.E., The protein data
bank, Nucl Acids Res, 28, 235–242 (2000)
4. Shaha Bhumi, Modia Palmi and Sagar Sneha R., In silico studies
on therapeutic agents for COVID-19: Drug repurposing approach,
Life Sci, 252, 117652 (2020)

Conclusion
The present study is to find out promising drug candidate for
COVID-19 from three Indian traditional medicinal plants
(ITMP) through different in silico virtual screening
protocols. At the end of in silico virtual screening, four
ligands such as Baloxavir marboxil from anti-viral drug
group, Formononetin-7-O-Glucuronide from Phyllanthus
niruri, Limocinin from Azadirachta indica and
Bisandrographolide from Andrographis paniculata were
chosen as drug candidate for COVID-19. These four drug
candidates for COVID-19 including three phytocompounds
from Indian Traditional Medicinal Plants (ITMP) have
shown good binding affinity towards SARS-CoV-2 protein
molecular targets and possess excellent drug likeliness,
pharmacokinetic, electrostatic potential profiles. The
conclusion of the present study is that these four compounds
could serve as promising drug candidates to control and fight
against COVID-19, if further elaborate research on clinical
trials is made using these drug molecules.
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Acknowledgement
The authors would like to thank Department of
Biotechnology, Sona College of Arts and Science, Salem
(Dt.)- 636 005, Tamil Nadu, India for their technical support.
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(Received 31st May 2020, accepted 02nd July 2020)