Ligands preparation and Target selection
In order to carry out the docking analysis, in the beginning the 3D structures of 49 ligands (natural compounds) out of 52 (Table1) were retrieved from PubChem Compound database and three ligands were modeled using ACD/Chem-Sketch. Many natural compounds reported to have biologically confirmed anti-SARS and anti-MERS coronavirus activity were identified [33], [34], [16], [17], [18], [19]. We have selected 21 medicinal plants that have anti-viral property (Table 1 & 4) and their compounds have high probability of directly inhibiting the COVID-19, perhaps providing immediate help in the treatment of the diseases which cause pneumonia.
The prospective targets were selected on the basis of functional categories of molecules: (1) The deubiquitinating enzyme PL-Pro that can reduce host anti-viral response [12], [13] (2) 3CLpro or main protease is important to the virus lifecycle [35]. (3) Spike binds to the cell membrane protein to enter human cells [14].These three targets provide a great opportunity to identify potential drug candidates for the treatment. COVID-19 3CL-Pro/M-Pro (PDB ID: 6LU7) [36] and Spike (PDB ID: 6vsb) [37] structures were retrieved from PDB data bank, whereas the structure of PL-Pro and IS-Spike was determined by Ab-initio modeling and homology modeling approach as the same was unavailable at PDB data bank. Energy minimization of all targeted 3D structure was done by YASARA server. Initial energy of the Spike, IS-Spike, M-Pro and PL-Pro protein were -135274.6, -378170.5, -126585.8 and 12117262.4 kJ/mol respectively while the end energy of the model is -146567.6, -534242.4,-166967.6 and -848519.5kJ/mol respectively. Energy minimization removes severe steric clashes between two atoms with a distance [30]. The 3D-Structure of COVID-19 retrieved as well as predicted model was further validated with PDBsum. Ramachandran plot analysis of the Spike, IS-Spike, M-Pro and PL-Pro model showed 83.7%, 86.2%, 91.7% and 74.7% residues come under favored region. The two model which are close to the requisite percentage of 90 for validating model which is near to good model, one cross to 90 i.e. good model, and one below 80 which come under average model. (Fig.2.). Favoured region residues varied between Spike and IS-Spike due to a change of A930V (24351C>T) in IS-Spike COVID-19 (Indian mutant Spike), which revealed that IS-Spike is more stable than general Spike protein. Favoured regions which showed in Ramachandran plot are energetically and sterically stable conformations of residues characterized by values of torsion angles ψ and ϕ. Mutant position in Ramachandran Plot for Predicting Protein Stability of Surface Mutations [38].
Docking studies
With the aim of findinga potential candidate for treating COVID-19, molecular docking studies were performed out the virtual screening of 52 ligands. Most of the molecules are active against different viral diseases viz. HIV, Influenza, Herpes, West Nile virus, and Dengue virus. The list of ligands tested for docking study is depicted in Table 1.
Protein-ligand interactions were also decoded with respect to nature of interacting amino acid residues and association of H-bonding. Binding of ligands to the target also indicates to the possibility that the ligand may be capable of ushering functional modulations in the target molecule [39], [40]. Most of the interacting amino acidic residues along with hydrogen bonding interactions shown by PatchDock analysis and further visualized by Discovery studio 3.5 (Fig.4- 7). The estimation of binding energy evaluation done by Hex8 to provide precious information that can be used to scrutinize the results of approving studies, for instance, in vitro, in vivo and clinical studies.
All 52 molecules were docked against the target enzyme COVID-19 and ranked based on their dock scores (Binding energy) and were depicted in Table3. In this table, we have mentioned the B.E of each molecule with Spike, IS-Spike, PL-Pro and M-Pro. The column average (avg.) B.E with Spike is avg. of Spike, PL-Pro and M-Pro. Similarly, the column avg. B.E with IS-Spike is avg. of IS-Spike, PL-Pro and M-Pro. Ranking is based on the avg. value of data, in which Rank1 indicates highest avg. binding energy with particular molecule and Rank 2 indicates lesser binding energy as compared to Ranked 1 molecule and so on. We have selected top 10 ligands which have high binding affinity to their targets i.e. Spike, IS-Spike, PL-Pro and M-Pro on the basis of binding energy (calculated by docking) and were depicted in Table2.The 10 leading ligands have high binding affinity for inhibition of Spike protein was Punicafolin (Phyllanthus emblica), Emblicanin A (Phyllanthus emblica), Lopinavir (Anti-HIV drugs), Punigluconin (Phyllanthus emblica), Kuwanon X (Morus alba), Rutin (Azadirachta indica), Phyllanemblinin A (Phyllanthus emblica), Lithospermic Acid (Salvia miltiorrhiza), Amaroswerin (Swertia chirata) and Heptacosanol (Eclipta prostrata).The standard drugs like Lopinavir, Hydroxychloroquinine and Ribavirin, which interact with Spike plus it come under 3, 15 and 21 rank out of 52. First 10 ligands have high binding affinity for inhibition of IS-Spike protein was Punigluconin (Phyllanthus emblica), Emblicanin A (Phyllanthus emblica), Rutin (Azadirachta indica), Lopinavir (Anti HIV drugs), Punicafolin (Phyllanthus emblica), Amarogentin (Swertia chirata), Azadirachtin (Azadirachta indica), Amaroswerin (Anti HIV drugs), Phyllanemblinin A (Phyllanthus emblica) and Lithospermic Acid (Salvia miltiorrhiza). The standard drugs such as Lopinavir, Hydroxychloroquinine and Ribavirin, which interact with Spike as well as they ranked on 4, 20 and 41. The 10 major ligands have high binding affinity for inhibition of PL-Pro protein was Punicafolin (Phyllanthus emblica), Emblicanin A (Phyllanthus emblica), Punigluconin (Phyllanthus emblica), Lopinavir (Anti HIV drugs), Phyllanemblinin A (Phyllanthus emblica), Amarogentin (Swertia chirata), Lithospermic Acid (Salvia miltiorrhiza), Azadirachtin (Azadirachta indica), Rutin (Azadirachta indica) and Amaroswerin (Swertia chirata). The standard drugs viz. Lopinavir, Hydroxychloroquinine and Ribavirin, which interact with PL-Pro and they ranked on 4, 20 and 41. The top 10 ligands have high binding affinity for inhibition of M-Pro protein was Punicafolin (Phyllanthus emblica), Emblicanin A (Phyllanthus emblica), Punigluconin (Phyllanthus emblica), Lopinavir (Anti HIV drugs), Kuwanon x (Morus alba), Rutin (Azadirachta indica), Lithospermic Acid (Salvia miltiorrhiza), Amaroswerin (Swertia chirata), Phyllanemblinin A (Phyllanthus emblica) and Amarogentin (Swertia chirata).The standard drugs i.e. Lopinavir, Hydroxychloroquinine and Ribavirin, which interact with M-Pro and it fall under rank 4, 24 and 43. The binding affinity of ligands with M-Pro and PL-Pro is better than Spike and IS-Spike so M-Pro and PL-Pro is better inhibitory target protein for inhibitory drugs. After comparative analysis of Spike and IS-Spike, we conclude that binding affinity of ligands with IS-Spike get low as compared to Spike so inhibitory potential of drugs may fragile (Table2 and 3).
Based on the avg. B.E with Spike, PL-Pro and M-Pro (Table3), we preferred best 10 ligands {Punicafolin (Phyllanthus emblica), Emblicanin A (Phyllanthus emblica), Punigluconin (Phyllanthus emblica), Lopinavir (Anti HIV drugs), Kuwanon X (Morus alba), Rutin (Azadirachta indica), Lithospermic Acid (Salvia miltiorrhiza), Phyllanemblinin A (Phyllanthus emblica), Amarogentin (Swertia chirata) and Amaroswerin (Swertia chirata)} for inhibition of all three targets (Spike, PL-Pro and M-Pro). On the basis of avg. B.E of IS-Spike, PL-Pro and M-Pro (Table3.), we favoured best 10 ligands {Punicafolin (Phyllanthus emblica), Emblicanin A (Phyllanthus emblica), Punigluconin (Phyllanthus emblica), Lopinavir (Anti HIV drugs) Rutin (Azadirachta indica), Amarogentin (Swertia chirata) and Amaroswerin (Swertia chirata), Phyllanemblinin A (Phyllanthus emblica), Lithospermic Acid (Salvia miltiorrhiza) and Kuwanon x (Morus alba) for inhibition of three targets (IS-Spike, PL-Pro and M-Pro). Based on the avg. B.E of Spike, PL-Pro and M-Pro as well as IS-Spike, PL-Pro and M-Pro, the standard drugs Lopinavir come under 4th rank, Hydroxychloroquine on 23rd rank and Ribavirin on 40th rank, out of 52 ligands.
In Table4, 49 compounds have been taken from 21 different medicinal plants and rests of three were standard drugs. Avg. value is calculated on the basis of each medicinal plant’s compound i.e.
We have ranked 21medicinal plants (possess 49 ligands) along with standard drugs (3 drugs) (Table4.) based on Avg. B.E (KJ/mol) with Spike, PL-Pro and M-Pro, and similarly ranked 21 medicinal plants (possess 49 ligands) along with standard drugs (3 drugs) (Table4) on the basis of Avg. B.E (KJ/mol) with Indian strain Spike, PL-Pro and M-Pro. From table 4 it is very clear that Malberry (Morus alba) is the most effective plant as compared to the other plants and standard drugs. While Amla (Phyllanthus emblica) is the second most effective medicinal plant. But in case of IS-Spike Amla (Phyllanthus emblica) is the most effective medicinal plant when compared with others.
There are four ligands out of top 10 whichare common in all four different networks and those come from Phyllanthus emblica (Amla) plus minimum one compound (Rutin) of Azadirachta indica ( Neem) out of 4 and a compound ( Amaroswerin ) of Swertia chirata, which is common in all networks. Moreover, a standard drug Lopinavir and a compound (Lithospermic Acid) of Salvia miltiorrhiza are common in all networks. Therefore, it looks logical that the compounds which are common in the entire network should have more inhibitory potential against COVID19 due to the better binding potential among all three target proteins including IS-Spike as displayed in Fig.3.
Table2. Comparative analysis of top 10 selected valuable ligands interacted with COVID-19 Spike, Indian mutant Spike, PL-Pro and M-Pro.
Top ran king
|
Molecular name
|
GCC
Spike
|
B.E
(KJ/mol
) of Spike
|
Molecular name
|
GCC
India n mut Spike
|
B.E
(KJ/mol
) of Indian
mutant
|
Molecular name
|
GCC PL-
Pro
|
B.E
(KJ/mol
) of PL- Pro
|
Molecular name
|
GCC M-
Pro
|
B.E
(KJ/mol
) of M- Pro
|
1
|
Punicafolin
|
6628
|
-293.66
|
Punigluconin
|
6736
|
-249.01
|
Punicafolin
|
7990
|
-452.28
|
Punicafolin
|
6878
|
-492.34
|
2
|
Emblicanin A
|
6336
|
-292.51
|
Emblicanin A
|
6794
|
-247.92
|
Emblicanin A
|
7056
|
-446.87
|
Emblicanin A
|
6380
|
-458
|
3
|
Lopinavir
|
7258
|
-280.47
|
Rutin
|
6354
|
-240.45
|
Punigluconin
|
7452
|
-434.4
|
Punigluconin
|
6492
|
-456.87
|
4
|
Punigluconin
|
6654
|
-274.05
|
Lopinavir
|
7524
|
-232.54
|
Lopinavir
|
8902
|
-394.06
|
Lopinavir
|
7070
|
-425.97
|
5
|
Kuwanon x
|
6256
|
-258
|
Punicafolin
|
7130
|
-229.36
|
Phyllanemblinin A
|
6826
|
-385.38
|
Kuwanon x
|
5768
|
-405.1
|
6
|
Rutin
|
6216
|
-242.48
|
Amarogentin
|
6356
|
-229.13
|
Amarogentin
|
7126
|
-383.64
|
Rutin
|
6156
|
-384.76
|
7
|
Phyllanemblinin A
|
6050
|
-234.85
|
Azadirachtin
|
6558
|
-225.95
|
Lithospermic Acid
|
6854
|
-383.13
|
Lithospermic Acid
|
5792
|
-373.81
|
8
|
Lithospermic Acid
|
5862
|
-233
|
Amaroswerin
|
6274
|
-223.9
|
Azadirachtin
|
6928
|
-377.57
|
Amaroswerin
|
5894
|
-368.89
|
9
|
Amaroswerin
|
6036
|
-230.98
|
Phyllanemblinin A
|
6072
|
-204.88
|
Rutin
|
7056
|
-367.75
|
Phyllanemblinin A
|
5744
|
-367.1
|
10
|
Heptacosanol
|
6270
|
-228.92
|
Lithospermic Acid
|
6104
|
-200.21
|
Amaroswerin
|
6858
|
-365.55
|
Amarogentin
|
5808
|
-365.34
|
Table3. Comparative docking study results on COVID-19 enzymes.
Sl.N
o.
|
Molecular name
|
Source/Std drugs
|
Common Name
|
B.E
(KJ/mol) of IS- Spike - Ligands
|
B.E
(KJ/mol) of Spike- Ligands
|
B.E
(KJ/mol) of PL- Pro- Ligands
|
B.E
(KJ/mol) of M-Pro- Ligands
|
Avg. B.E
(KJ/mol
) with Spike
|
Rank
|
Avg.
B.E(KJ/mol)with IS- Spike
|
Rank
|
1
|
Punicafolin
|
Phyllanthus emblica
|
Amla
|
-229.36
|
-293.66
|
-452.28
|
-492.34
|
-412.76
|
1
|
-391.33
|
1
|
2
|
Emblicanin A
|
Phyllanthus emblica
|
Amla
|
-247.92
|
-292.51
|
-446.87
|
-458
|
-399.13
|
2
|
-384.26
|
2
|
3
|
Punigluconin
|
Phyllanthus emblica
|
Amla
|
-249.01
|
-274.05
|
-434.4
|
-456.87
|
-388.44
|
3
|
-380.09
|
3
|
4
|
Lopinavir
|
Anti HIV drugs
|
Anti HIV drugs
|
-232.54
|
-280.47
|
-394.06
|
-425.97
|
-366.83
|
4
|
-350.86
|
4
|
5
|
Kuwanon x
|
Morus alba
|
Mulberry
|
-192.23
|
-258
|
-358.03
|
-405.1
|
-340.38
|
5
|
-318.45
|
10
|
6
|
Rutin
|
Azadirachta indica
|
Neem
|
-240.45
|
-242.48
|
-367.75
|
-384.76
|
-331.66
|
6
|
-330.99
|
5
|
7
|
Lithospermic Acid
|
Salvia miltiorrhiza
|
Red sage
|
-200.21
|
-233
|
-383.13
|
-373.81
|
-329.98
|
7
|
-319.05
|
9
|
8
|
Phyllanemblinin A
|
Phyllanthus emblica
|
Amla
|
-204.88
|
-234.85
|
-385.38
|
-367.1
|
-329.11
|
8
|
-319.12
|
8
|
9
|
Amarogentin
|
Swertia chirata
|
Chirayta
|
-229.13
|
-221.5
|
-383.64
|
-365.34
|
-323.49
|
9
|
-326.04
|
6
|
10
|
Amaroswerin
|
Swertia chirata
|
Chirayta
|
-223.9
|
-230.98
|
-365.55
|
-368.89
|
-321.81
|
10
|
-319.45
|
7
|
11
|
Azadirachtin
|
Azadirachta indica
|
Neem
|
-225.95
|
-224.46
|
-377.57
|
-342.81
|
-314.95
|
11
|
-315.44
|
11
|
12
|
Isoquercitrin
|
Houttuynia cordata
|
Fish mint
|
-186.09
|
-205.32
|
-326.61
|
-315.76
|
-282.56
|
12
|
-276.15
|
13
|
13
|
Hentriacontanol
|
Eclipta prostrata
|
Bhringraj
|
-169.78
|
-217.03
|
-284.14
|
-344.52
|
-281.90
|
13
|
-266.15
|
18
|
14
|
Nimbaflavone
|
Azadirachta indica
|
Neem
|
-199.83
|
-212
|
-321.59
|
-311.62
|
-281.74
|
14
|
-277.68
|
12
|
15
|
Heptacosanol
|
Eclipta prostrata
|
Bhringraj
|
-170.01
|
-228.92
|
-284.14
|
-326.21
|
-279.76
|
15
|
-260.12
|
21
|
16
|
Hyperoside
|
Azadirachta indica
|
Neem
|
-188.14
|
-192.9
|
-328.47
|
-309
|
-276.79
|
16
|
-275.20
|
14
|
17
|
Thalimonine
|
Thalictrum simplex L.
|
Meadow rue
|
-141.45
|
-225.37
|
-298.63
|
-304.7
|
-276.23
|
17
|
-248.26
|
24
|
18
|
Baicalin
|
Scutellaria
baicalensis
|
Baikal skullcap
|
-192.07
|
-195.01
|
-325.29
|
-304.64
|
-274.98
|
18
|
-274.00
|
16
|
19
|
Stigmasterol
|
Eclipta prostrata
|
Bhringraj
|
-184.59
|
-184.29
|
-333.34
|
-301.94
|
-273.19
|
19
|
-273.29
|
17
|
20
|
Quercitrin
|
Houttuynia cordata
|
Fish mint
|
-184.69
|
-170.57
|
-340.69
|
-296.85
|
-269.37
|
20
|
-274.08
|
15
|
21
|
Betulinic acid
|
Symplocos racemosa
|
Lodhra
|
-152.89
|
-191.59
|
-318.5
|
-295.43
|
-268.51
|
21
|
-255.61
|
22
|
22
|
Curcumin
|
Curcuma longa
|
Turmeric
|
-182.11
|
-193.64
|
-290.36
|
-316
|
-266.67
|
22
|
-262.82
|
19
|
23
|
Hydroxychloroquine
|
Anti Malarian drug
|
Anti Malarian drug
|
-174.59
|
-212.31
|
-302.02
|
-284.17
|
-266.17
|
23
|
-253.59
|
23
|
24
|
Mangiferin
|
Swertia chirata
|
Chirayta
|
-186.26
|
-179.78
|
-306.83
|
-287.63
|
-258.08
|
24
|
-260.24
|
20
|
25
|
Calanolide A
|
Calophyllum Spp
|
Indian doomba oil
tree
|
-153.69
|
-192.85
|
-292.69
|
-281.06
|
-255.53
|
25
|
-242.48
|
27
|
26
|
Gentiopicrin
|
Swertia chirata
|
Chirayta
|
-146.31
|
-207.26
|
-275.75
|
-269.6
|
-250.87
|
26
|
-230.55
|
34
|
27
|
Flavonoid
|
Phyllanthus emblica
|
Amla
|
-157.89
|
-181.39
|
-301.3
|
-269.49
|
-250.73
|
27
|
-242.89
|
25
|
28
|
Tinosoprin A
|
Tinospora cordifolia
|
Giloy
|
-133.77
|
-162.75
|
-289.3
|
-279.49
|
-243.85
|
28
|
-234.19
|
29
|
29
|
Sweroside
|
Swertia chirata
|
Chirayta
|
-138.76
|
-171.44
|
-273.27
|
-280.21
|
-241.64
|
29
|
-230.75
|
33
|
30
|
Piperine
|
Piper longum
|
Indian long
pepper
|
-142.25
|
-170.94
|
-273.36
|
-277.91
|
-240.74
|
30
|
-231.17
|
32
|
31
|
Piper longumine
|
Piper longum
|
Indian long
pepper
|
-158.25
|
-149.86
|
-285.96
|
-283.55
|
-239.79
|
31
|
-242.59
|
26
|
32
|
Swertiamarin
|
Swertia chirata
|
Chirayta
|
-150.87
|
-168.53
|
-274.78
|
-273.88
|
-239.06
|
32
|
-233.18
|
30
|
33
|
Quercitin
|
Houttuynia cordata
|
Fish mint
|
-128.81
|
-211.98
|
-245.18
|
-259.05
|
-238.74
|
33
|
-211.01
|
37
|
34
|
Kaempferol
|
Phyllanthus emblica
|
Amla
|
-129.74
|
-205.25
|
-248.38
|
-251.81
|
-235.15
|
34
|
-209.98
|
38
|
35
|
Palmatine
|
Tinospora cordifolia
|
Giloy
|
-151.54
|
-157.84
|
-279.53
|
-265.39
|
-234.25
|
35
|
-232.15
|
31
|
36
|
Jatorrohizine
|
Tinospora cordifolia
|
Giloy
|
-166.22
|
-156.13
|
-281.01
|
-263.65
|
-233.60
|
36
|
-236.96
|
28
|
37
|
Berberine
|
Tinospora cordifolia
|
Giloy
|
-138.6
|
-146.84
|
-271.59
|
-278.24
|
-232.22
|
37
|
-229.48
|
36
|
38
|
Magnoflorine
|
Tinospora cordifolia
|
Giloy
|
-156.05
|
-160.59
|
-272.87
|
-260.3
|
-231.25
|
38
|
-229.74
|
35
|
39
|
Resveratrol
|
Veratrum
grandiflorum
|
Corn lilies
|
-117.42
|
-184.25
|
-250.46
|
-237.71
|
-224.14
|
39
|
-201.86
|
39
|
40
|
Ribavirin
|
Anti HIV drugs
|
Anti HIV drugs
|
-114.61
|
-195.18
|
-227.72
|
-211.73
|
-211.54
|
40
|
-184.69
|
40
|
41
|
Zingerone
|
Zingiber officinale
|
Ginger
|
-100.47
|
-185
|
-235.15
|
-207.5
|
-209.22
|
41
|
-181.04
|
43
|
42
|
DesmethylWeddolact
one
|
Eclipta prostrata
|
Bhringraj
|
-96.6
|
-185.82
|
-208.98
|
-208.54
|
-201.11
|
42
|
-171.37
|
45
|
43
|
Weddolactone
|
Eclipta prostrata
|
Bhringraj
|
-105.33
|
-174.16
|
-205.3
|
-213.9
|
-197.79
|
43
|
-174.84
|
44
|
44
|
Ajoene
|
Allium sativum L.
|
Garlic
|
-105.18
|
-149.54
|
-209.93
|
-232.46
|
-197.31
|
44
|
-182.52
|
41
|
45
|
Harmine
|
Peganum harmala
|
Wild rue
|
-115.55
|
-151.01
|
-208.06
|
-220.17
|
-193.08
|
45
|
-181.26
|
42
|
46
|
Bicyclogermacrene
|
Glechon marifolia
|
Mint
|
-109.44
|
-159.85
|
-190.79
|
-201.21
|
-183.95
|
46
|
-167.15
|
46
|
47
|
Eugenol
|
Eugenia caryophyllus
|
Clove
|
-86.04
|
-153.97
|
-206.73
|
-180.5
|
-180.40
|
47
|
-157.76
|
47
|
48
|
S-Allyl-L-cysteine
|
Allium sativum L
|
Garlic
|
-80.79
|
-170.4
|
-183.93
|
-177.61
|
-177.31
|
48
|
-147.44
|
49
|
49
|
Diallyltrisulfide
(DTS)
|
Allium sativum L.
|
Garlic
|
-74.79
|
-136.08
|
-182.24
|
-189.51
|
-169.28
|
49
|
-148.85
|
48
|
50
|
Allicin
|
Allium sativum L.
|
Garlic
|
-80.28
|
-148.56
|
-166.1
|
-190.38
|
-168.35
|
50
|
-145.59
|
50
|
51
|
Homonojirimycin
|
Omphalea diandra
|
Omphalea
diandra
|
-80.02
|
-155.81
|
-169.44
|
-174.27
|
-166.51
|
51
|
-141.24
|
51
|
52
|
Diallyl
disulfide(DDS)
|
Allium sativum L.
|
Garlic
|
-75.21
|
-126.93
|
-161.81
|
-181.93
|
-156.89
|
52
|
-139.65
|
52
|
Table4. Comparative analysis of 21 medicinal plants along with standard drugs screened for effective medicinal plants as compared to standard drugs.
Common Name
|
Pharmacological function
|
References
|
total compoun d for this study
|
Avg. B.E
(KJ/mol) with Spike
|
Rank
|
Avg. B.E
(KJ/mol) with IS- Spike
|
Rank
|
Mulberry
|
Anti-viral
|
([41]
|
1
|
-340.38
|
1
|
-318.45
|
3
|
Amla
|
Anti-viral, Antiyretic, Analgesic, Antitussive,
Antiatherogeric
|
[42]
|
6
|
-335.89
|
2
|
-321.28
|
1
|
Red sage
|
Anti-viral
|
[43]
|
1
|
-329.98
|
3
|
-319.05
|
2
|
Neem
|
Anti-viral
|
[44]
|
4
|
-301.28
|
4
|
-299.83
|
4
|
Anti HIV drugs
|
Anti-viral
|
[45]
|
2
|
-289.19
|
5
|
-267.77
|
6
|
Meadow rue
|
Anti-Influenza
|
[46]
|
1
|
-276.23
|
6
|
-248.26
|
12
|
Baikal skullcap
|
Anti-viral
|
[47]
|
1
|
-274.98
|
7
|
-274.00
|
5
|
Chirayta
|
Anti-viral, Antifungal, Antiinflamatory & Anticancer
|
[48]
|
6
|
-272.49
|
8
|
-266.70
|
7
|
Lodhra
|
Anti-viral
|
[49]
|
1
|
-268.51
|
9
|
-255.61
|
9
|
Turmeric
|
Anti-viral
|
[50]
|
1
|
-266.67
|
10
|
-262.82
|
8
|
Anti Malarian drug
|
Anti-viral
|
[51]
|
1
|
-266.17
|
11
|
-253.59
|
11
|
Fish mint
|
Anti-viral & Immuno stimulant
|
[52]
|
3
|
-263.56
|
12
|
-253.75
|
10
|
Indian doomba oil
tree
|
Anti-HIV
|
[53]
|
1
|
-255.53
|
13
|
-242.48
|
13
|
Bhringraj
|
Anti-viral, Anti-oxidant, Antianalgesic & Antibacterial
|
[54]
|
5
|
-246.75
|
14
|
-229.15
|
16
|
Indian long pepper
|
Anti-viral
|
[34]
|
2
|
-240.26
|
15
|
-236.88
|
14
|
Giloy
|
Anti-HIV, Antipyretic,Anti-inflammatory
|
[55]
|
5
|
-235.03
|
16
|
-232.50
|
15
|
Corn lilies
|
Anti-viral
|
[56]
|
1
|
-224.14
|
17
|
-201.86
|
17
|
Ginger
|
Anti-viral
|
[57]
|
1
|
-209.22
|
18
|
-181.04
|
19
|
Wild rue
|
Anti-viral
|
[58]
|
1
|
-193.08
|
19
|
-181.26
|
18
|
Mint
|
Anti-viral & Antifungal
|
[59]
|
1
|
-183.95
|
20
|
-167.15
|
20
|
Clove
|
Anti-viral, Antifungal & Antibacterial
|
[60]
|
1
|
-180.40
|
21
|
-157.76
|
21
|
Garlic
|
Antiviral, Antimicrobial, Reduce risk of cardiovascular
diseases
|
[61]
|
5
|
-173.83
|
22
|
-152.81
|
22
|
Omphalea diandra
|
Anti-viral
|
[62]
|
1
|
-166.51
|
23
|
-141.24
|
23
|