Metagenome, having accession number SRR10017187, for West Nile virus was downloaded from SRA database.
As, per Per base sequence quality results of FASTQC and MultiQC, the sequence quality is not good hence we go ahead with trimming the sequence.
CUTADAPT tool [27] is used for trimming. It finds and removes adapter sequences, primers, poly-A tails, and other types of unwanted sequence from our data. It searches for the adapter in all reads and removes it when it finds it. Further, sequence quality of the cutadapt output is checked using FASTQC and MultiQC and it is found within the range.
SortMeRNA tool removes any reads identified as rRNA from our dataset. Fastq Interlace tool joins paired end FASTQ reads from two separate files. Taxonomic profiling [28] was done using MetaPhlAn tool (Fig. 1, Table 1). The output is visualized using Krona and Graphlan (Fig. 2).
Table 1
MetaPhlAn: Predicted taxon relative abundances at each taxonomic levels
After generation of taxonomy, we move to functional information of our microbiome. Functional information of the above microbiome community [28] was done using HUMAnN pipeline (Table 2).
Table 2
Functional information of microbiome
# Gene Family
|
humann_Abundance-RELAB
|
UNMAPPED
|
0.888769
|
UniRef90_D9MXB1
|
0.0073362
|
UniRef90_D9MXB1|unclassified
|
0.0073362
|
UniRef90_UPI0001DD3770
|
0.00495637
|
UniRef90_UPI0001DD3770|unclassified
|
0.00495637
|
UniRef90_A0A1B1WW31
|
0.00484378
|
UniRef90_A0A1B1WW31|unclassified
|
0.00484378
|
UniRef90_B9DF73
|
0.00459488
|
UniRef90_B9DF73|unclassified
|
0.00459488
|
UniRef90_A0A067ZQ74
|
0.00422115
|
UniRef90_A0A067ZQ74|unclassified
|
0.00422115
|
UniRef90_A0A077EZ14
|
0.00417222
|
UniRef90_A0A077EZ14|unclassified
|
0.00417222
|
UniRef90_A0A067ZS80
|
0.00390475
|
UniRef90_A0A067ZS80|unclassified
|
0.00390475
|
UniRef90_UPI0003F054D7
|
0.00376104
|
UniRef90_UPI0003F054D7|unclassified
|
0.00376104
|
UniRef90_F1BA45
|
0.0036982
|
UniRef90_F1BA45|unclassified
|
0.0036982
|
UniRef90_A0A1X3CH90
|
0.00318336
|
UniRef90_A0A1X3CH90|unclassified
|
0.00318336
|
UniRef90_UPI000D0C92C0
|
0.00302072
|
UniRef90_UPI000D0C92C0|unclassified
|
0.00302072
|
UniRef90_K9L2G3
|
0.00265002
|
UniRef90_K9L2G3|unclassified
|
0.00265002
|
UniRef90_A0A1B1WWN4
|
0.00258533
|
UniRef90_A0A1B1WWN4|unclassified
|
0.00258533
|
UniRef90_K7ET80
|
0.00256502
|
UniRef90_K7ET80|unclassified
|
0.00256502
|
UniRef90_Q91CD9
|
0.00251161
|
UniRef90_Q91CD9|unclassified
|
0.00251161
|
UniRef90_UPI00018E17CF
|
0.00240202
|
UniRef90_UPI00018E17CF|unclassified
|
0.00240202
|
UniRef90_G7PXF9
|
0.00234066
|
UniRef90_G7PXF9|unclassified
|
0.00234066
|
UniRef90_F6Z663
|
0.00218081
|
UniRef90_F6Z663|unclassified
|
0.00218081
|
UniRef90_G7MFM1
|
0.00215974
|
UniRef90_G7MFM1|unclassified
|
0.00215974
|
UniRef90_A0A2K6NB76
|
0.0020891
|
UniRef90_A0A2K6NB76|unclassified
|
0.0020891
|
UniRef90_UPI000181CCFE
|
0.00203554
|
UniRef90_UPI000181CCFE|unclassified
|
0.00203554
|
UniRef90_C9WPK8
|
0.00195453
|
UniRef90_C9WPK8|unclassified
|
0.00195453
|
UniRef90_P14335
|
0.00180304
|
UniRef90_P14335|unclassified
|
0.00180304
|
UniRef90_F7HJ82
|
0.00180269
|
UniRef90_F7HJ82|unclassified
|
0.00180269
|
UniRef90_A0A0D3MDX0
|
0.00160595
|
UniRef90_A0A0D3MDX0|unclassified
|
0.00160595
|
UniRef90_UPI0000E69E2F
|
0.00153697
|
UniRef90_UPI0000E69E2F|unclassified
|
0.00153697
|
UniRef90_I3VPR6
|
0.00149368
|
UniRef90_I3VPR6|unclassified
|
0.00149368
|
UniRef90_G8E0A9
|
0.00146336
|
UniRef90_G8E0A9|unclassified
|
0.00146336
|
UniRef90_D3X888
|
0.0013421
|
UniRef90_D3X888|unclassified
|
0.0013421
|
UniRef90_UPI00003BECBC
|
0.00130469
|
UniRef90_UPI00003BECBC|unclassified
|
0.00130469
|
UniRef90_UPI0002C39258
|
0.00127138
|
UniRef90_UPI0002C39258|unclassified
|
0.00127138
|
UniRef90_Q6VXX6
|
0.00120319
|
UniRef90_Q6VXX6|unclassified
|
0.00120319
|
UniRef90_D3X8F1
|
0.0011535
|
UniRef90_D3X8F1|unclassified
|
0.0011535
|
UniRef90_A0A1S6WNB4
|
0.00110115
|
UniRef90_A0A1S6WNB4|unclassified
|
0.00110115
|
UniRef90_D3X8F7
|
0.00102768
|
UniRef90_D3X8F7|unclassified
|
0.00102768
|
UniRef90_D3X8D8
|
0.000998791
|
UniRef90_D3X8D8|unclassified
|
0.000998791
|
UniRef90_Q91KP3
|
0.000989086
|
UniRef90_Q91KP3|unclassified
|
0.000989086
|
UniRef90_D9IFF5
|
0.000952321
|
UniRef90_D9IFF5|unclassified
|
0.000952321
|
UniRef90_F7EY45
|
0.000912381
|
UniRef90_F7EY45|unclassified
|
0.000912381
|
UniRef90_D5K1B9
|
0.00090469
|
UniRef90_D5K1B9|unclassified
|
0.00090469
|
UniRef90_Q67428
|
0.000861045
|
UniRef90_Q67428|unclassified
|
0.000861045
|
UniRef90_Q91AB0
|
0.000854561
|
UniRef90_Q91AB0|unclassified
|
0.000854561
|
UniRef90_D3X875
|
0.000850089
|
UniRef90_D3X875|unclassified
|
0.000850089
|
UniRef90_A0A2K5WQL4
|
0.000795493
|
UniRef90_A0A2K5WQL4|unclassified
|
0.000795493
|
UniRef90_B1P6F1
|
0.000689513
|
UniRef90_B1P6F1|unclassified
|
0.000689513
|
UniRef90_P29984
|
0.000618302
|
UniRef90_P29984|unclassified
|
0.000618302
|
UniRef90_A0A0B5H4C4
|
0.000582165
|
UniRef90_A0A0B5H4C4|unclassified
|
0.000582165
|
UniRef90_Q6YFU6
|
0.00051542
|
UniRef90_Q6YFU6|unclassified
|
0.00051542
|
UniRef90_A0A0P0RST2
|
0.000505187
|
UniRef90_A0A0P0RST2|unclassified
|
0.000505187
|
UniRef90_A0A0D5CWD5
|
0.000489091
|
UniRef90_A0A0D5CWD5|unclassified
|
0.000489091
|
UniRef90_A0A068AXW2
|
0.000463204
|
UniRef90_A0A068AXW2|unclassified
|
0.000463204
|
UniRef90_A0A1X3CWX3
|
0.000451315
|
UniRef90_A0A1X3CWX3|unclassified
|
0.000451315
|
UniRef90_I1TEC3
|
0.000443267
|
UniRef90_I1TEC3|unclassified
|
0.000443267
|
UniRef90_A0A229QXW6
|
0.000390111
|
UniRef90_A0A229QXW6|unclassified
|
0.000390111
|
UniRef90_UPI0000485C0B
|
0.000373856
|
UniRef90_UPI0000485C0B|unclassified
|
0.000373856
|
UniRef90_Q6VXX7
|
0.000367549
|
UniRef90_Q6VXX7|unclassified
|
0.000367549
|
UniRef90_H2NBX3
|
0.000356109
|
UniRef90_H2NBX3|unclassified
|
0.000356109
|
UniRef90_UPI000642CDD8
|
0.000349761
|
UniRef90_UPI000642CDD8|unclassified
|
0.000349761
|
UniRef90_I3N2P9
|
0.000333919
|
UniRef90_I3N2P9|unclassified
|
0.000333919
|
UniRef90_D9IFG5
|
0.000299914
|
UniRef90_D9IFG5|unclassified
|
0.000299914
|
UniRef90_D3X874
|
0.000283626
|
UniRef90_D3X874|unclassified
|
0.000283626
|
UniRef90_Q9DP92
|
0.000282183
|
UniRef90_Q9DP92|unclassified
|
0.000282183
|
UniRef90_D3X8B2
|
0.000279068
|
UniRef90_D3X8B2|unclassified
|
0.000279068
|
UniRef90_A0A075FC35
|
0.000211602
|
UniRef90_A0A075FC35|unclassified
|
0.000211602
|
UniRef90_B7U2U9
|
0.000200363
|
UniRef90_B7U2U9|unclassified
|
0.000200363
|
UniRef90_C9WPM0
|
0.000194638
|
UniRef90_C9WPM0|unclassified
|
0.000194638
|
UniRef90_A0A0P7UTC2
|
0.000191691
|
UniRef90_A0A0P7UTC2|unclassified
|
0.000191691
|
UniRef90_F7FBV8
|
0.000191691
|
UniRef90_F7FBV8|unclassified
|
0.000191691
|
UniRef90_G3SQL6
|
0.000191691
|
UniRef90_G3SQL6|unclassified
|
0.000191691
|
UniRef90_H3BYH5
|
0.000191691
|
UniRef90_H3BYH5|unclassified
|
0.000191691
|
UniRef90_P60866
|
0.000191691
|
UniRef90_P60866|unclassified
|
0.000191691
|
UniRef90_D3X8C7
|
0.000186455
|
UniRef90_D3X8C7|unclassified
|
0.000186455
|
UniRef90_A0A2K6EGR5
|
0.000170037
|
UniRef90_A0A2K6EGR5|unclassified
|
0.000170037
|
UniRef90_A0A0B7JKQ7
|
0.000166418
|
UniRef90_A0A0B7JKQ7|unclassified
|
0.000166418
|
UniRef90_UPI0005215E94
|
0.000165638
|
UniRef90_UPI0005215E94|unclassified
|
0.000165638
|
UniRef90_G3I2D3
|
0.00016095
|
UniRef90_G3I2D3|unclassified
|
0.00016095
|
UniRef90_A0A2I0MVY6
|
0.000152329
|
UniRef90_A0A2I0MVY6|unclassified
|
0.000152329
|
UniRef90_L9LBB7
|
0.000143369
|
UniRef90_L9LBB7|unclassified
|
0.000143369
|
UniRef90_UPI0006B0C551
|
0.000133289
|
UniRef90_UPI0006B0C551|unclassified
|
0.000133289
|
UniRef90_A0A091DCD6
|
0.000130236
|
UniRef90_A0A091DCD6|unclassified
|
0.000130236
|
UniRef90_UPI000D3231B4
|
0.00012363
|
UniRef90_UPI000D3231B4|unclassified
|
0.00012363
|
UniRef90_UPI000359548B
|
0.000119308
|
UniRef90_UPI000359548B|unclassified
|
0.000119308
|
UniRef90_UPI00051F13F9
|
0.000116856
|
UniRef90_UPI00051F13F9|unclassified
|
0.000116856
|
UniRef90_UPI0005216B30
|
0.000112244
|
UniRef90_UPI0005216B30|unclassified
|
0.000112244
|
UniRef90_K7P5A3
|
0.000108977
|
UniRef90_K7P5A3|unclassified
|
0.000108977
|
UniRef90_L5JTI1
|
8.00319e-05
|
UniRef90_L5JTI1|unclassified
|
8.00319e-05
|
UniRef90_Q6VYH3
|
7.08503e-05
|
UniRef90_Q6VYH3|unclassified
|
7.08503e-05
|
UniRef90_A0A2U3XJL7
|
5.7032e-05
|
UniRef90_A0A2U3XJL7|unclassified
|
5.7032e-05
|
Next, from the gene family information, we obtain the functional information of our microbiome using Superfamily server. The Functional information of 1st five families from Normalized gene families as detected by Superfamily (HMM library and genome assignments server) is given below (Fig. 3).
As per the information obtained from Superfamily database it is seen that the Domain D9MXB1 is seen in the region 296-430 and 3-284 of the superfamily P-loop containing nucleoside triphosphate hydrolases and in the Family of RNA helicase.
A0A1B1WW31 domain, Region 1 at position 291-590, and of the superfamily Viral glycoprotein, central and dimerisation domains of Family Viral glycoprotein, central and dimerisation domains, 2 Region 2 at position 1990-2124 corrosponds to Superfamily P-loop containing nucleoside triphosphate hydrolases and Family RNA helicase and Region 3's position 582-696 Superfamily E set domains with Family of Class II viral fusion proteins C-terminal domain.
B9DF73 Domain is included in Region 1 at position 670-996 and 1024-1247 of the Superfamily DNA/RNA polymerases Family RNA-dependent RNA-polymerase. 2nd Region at postion 370-621 of the Superfamily S-adenosyl-L-methionine-dependent methyltransferases and Family mRNA cap methylase.
A0A067ZQ74 Domain's 1st Region at 2831-3157, 3185-3408 of Superfamily DNA/RNA polymerases of Family RNA-dependent RNA-polymerase. 2nd Region at 291-590 of Superfamily Viral glycoprotein, central and dimerisation domains of Family Viral glycoprotein, central and dimerisation. 3rd Region at 1990-2124 of Superfamily P-loop containing nucleoside triphosphate hydrolases in the Family RNA helicase. 4th Region at 582-696 of Superfamily E set domains of Family Class II viral fusion proteins C-terminal domain. 5th Region at 1687-1978 of Superfamily P-loop containing nucleoside triphosphate hydrolases of the Family RNA helicase. 6th Region at 1510-1676 of the Superfamily Trypsin-like serine proteases of Family Viral proteases. 7th Region at 22-99 of Superfamily Flavivirus capsid protein C of Family Flavivirus capsid protein C and 8th Region of Superfamily S-adenosyl-L-methionine-dependent methyltransferases of FamilymRNA cap methylase.
A0A077EZ14 Domain's 1 Region at 485-619 of the Superfamily P-loop containing nucleoside triphosphate hydrolases of Family RNA helicase. Region 2 at 182-473 of Superfamily P-loop containing nucleoside triphosphate hydrolases of Family RNA helicase and Region 3 at 5-171 of Superfamily Trypsin-like serine proteases of Family Viral proteases.
Structure based drug designing of West Nile Fever
Since, West Nile feveris a mosquito-borne disease, we further go ahead towards designing novel drug for the disease. From the MetaPhlAn: Bowtie2 output we get the gene ids. Corresponding gene receptors are taken from NCBI for our work (Table 3).
Table 3
Genes with their NCBI Accession number
Sl. No
|
Gene Receptors
|
NCBI Accession Number
|
Homologous Template
|
1.
|
CCR5
|
AAB57793.1
|
4MBS
|
2
|
CLEC4M
|
AAI10615.1
|
1SL6
|
3
|
IFITM2
|
CAG33175.1
|
3WXX
|
4
|
IRF3
|
AAH71721.1
|
7JFM
|
Abbreviations of genes:
- CCR5: C-C Motif Chemokine Receptor 5
- CLEC4M: C-Type Lectin Domain Family 4 Member M
- IFITM2: Interferon Induced Transmembrane Protein 2
- IRF3: Interferon Regulatory Factor 3
Homology modeling
Homology modeling of the above receptors are done using SWISS-MODEL server. The receptor model and corresponding ramachandran plot results are given in Fig. 4. Template used for modeling is given in Table 3.
Ayurvedic Medicinal plants Ginkgo biloba, Uncaria tomentosa, Lycoris radiate and Glycyrrhiza glabra are traditionally used to treat many diseases, such as respiratory disorders and fever. The potency of their phytocompounds in treating West Nile Fever is studied here.
As per Lipinski’s rule of five [ADME(Adsorption, distribution and metabolism extraction)] we check the drug likeliness of the above phytocompounds (Table 4-7).
Table 4
ADME studies of Ginkgo biloba
SL.
NO
|
Compounds
|
Mi
Log p
|
TSPA
|
Natoms
|
mw
|
nON
|
nOHNH
|
N-Violations
|
nROTB
|
VOLUME
|
1
|
Ginkgolide A
|
-1.46
|
128.60
|
29
|
408.40
|
9
|
2
|
0
|
1
|
339.84
|
2
|
Ginkgolide B
|
-2.38
|
148.83
|
30
|
424.40
|
10
|
3
|
0
|
1
|
347.88
|
3
|
Ginkgolide C
|
-3.29
|
169.06
|
31
|
440.40
|
11
|
4
|
1
|
1
|
355.93
|
4
|
Isorhamnetin
|
1.99
|
120.36
|
23
|
316.26
|
7
|
4
|
0
|
2
|
257.61
|
5
|
Quercetin
|
1.68
|
131.35
|
22
|
302.24
|
7
|
5
|
0
|
1
|
240.08
|
6
|
Protocatechuic acid.
|
2.10
|
118.21
|
20
|
276.24
|
6
|
5
|
0
|
3
|
231.33
|
7
|
Luteolin
|
1.97
|
111.12
|
21
|
286.24
|
6
|
4
|
0
|
1
|
232.07
|
Table 5
ADME studies ofUncaria tomentosa
SL.
NO
|
Compounds
|
Mi
Log p
|
TSPA
|
Natoms
|
mw
|
nO
N
|
nOHNH
|
N
Violations
|
nROTB
|
VOLUME
|
1
|
Uncarine C
|
2.18
|
67.88
|
27
|
368.43
|
6
|
1
|
0
|
2
|
333.36
|
2
|
Ajmalicine
|
3.41
|
54.57
|
26
|
352.43
|
5
|
1
|
0
|
2
|
325.29
|
3
|
Isomitraphylline
|
2.18
|
67.88
|
27
|
368.43
|
6
|
1
|
0
|
2
|
333.36
|
4
|
Isopteropodine
|
2.18
|
67.88
|
27
|
368.43
|
6
|
1
|
0
|
2
|
333.36
|
5
|
Mitraphylline
|
2.18
|
67.88
|
27
|
368.43
|
6
|
1
|
0
|
2
|
333.36
|
6
|
Isorhynchophylline
|
2.83
|
67.88
|
28
|
384.48
|
6
|
1
|
0
|
5
|
360.74
|
7
|
Speciophylline
|
2.18
|
67.88
|
27
|
368.43
|
6
|
1
|
0
|
2
|
333.36
|
Table 6
ADME studies ofLycoris radiata
SL.
NO
|
Compounds
|
Mi
Log p
|
TSPA
|
Natoms
|
mw
|
nON
|
nOHNH
|
N
Violations
|
nROTB
|
VOLUME
|
1
|
Caranine
|
1.45
|
41.93
|
20
|
271.32
|
4
|
1
|
0
|
0
|
241.36
|
2
|
galanthamine
|
1.54
|
41.93
|
21
|
287.36
|
4
|
1
|
0
|
1
|
268.19
|
3
|
Hippeastrine.
|
1.23
|
68.24
|
23
|
315.32
|
6
|
1
|
0
|
0
|
269.11
|
4
|
Homolycorine
|
1.90
|
48.01
|
23
|
315.37
|
5
|
0
|
0
|
2
|
288.23
|
5
|
Lycoramine
|
1.56
|
41.93
|
21
|
289.38
|
4
|
1
|
0
|
1
|
274.38
|
6
|
lycorine
|
0.54
|
62.16
|
21
|
287.31
|
5
|
2
|
0
|
0
|
249.40
|
7
|
Tazettine
|
-2.45
|
57.16
|
25
|
346.40
|
6
|
1
|
0
|
1
|
311.82
|
Table 7
ADME studies ofGlycyrrhiza glabra
SL.
NO
|
Compounds
|
Mi
Log p
|
TSPA
|
Natoms
|
mw
|
nON
|
nOHNH
|
N
Violations
|
nROTB
|
VOLUME
|
1
|
phloretin
|
2.66
|
97.98
|
20
|
274.27
|
5
|
4
|
0
|
4
|
240.11
|
2
|
Rosmarinic acid
|
1.63
|
144.52
|
26
|
360.32
|
8
|
5
|
0
|
7
|
303.54
|
3
|
Isocoumarin
|
1.82
|
30.21
|
11
|
146.15
|
2
|
0
|
0
|
0
|
128.59
|
4
|
Cortison
|
1.43
|
91.67
|
26
|
360.45
|
5
|
2
|
0
|
2
|
337.20
|
5
|
|
2.20
|
66.76
|
19
|
256.26
|
4
|
2
|
0
|
1
|
222.24
|
6
|
Liquiritin
|
0.41
|
145.91
|
30
|
418.40
|
9
|
5
|
0
|
4
|
354.37
|
7
|
Glabridin
|
4.20
|
58.92
|
24
|
324.38
|
4
|
2
|
0
|
1
|
295.25
|
8
|
Chlorozotocin
|
-1.48
|
159.75
|
20
|
313.69
|
10
|
5
|
0
|
9
|
253.94
|
9
|
hispaglabridinA
|
6.24
|
58.92
|
29
|
392.50
|
4
|
2
|
1
|
3
|
372.59
|
10
|
Isoliquiritin
|
0.98
|
156.91
|
30
|
418.40
|
9
|
6
|
1
|
6
|
358.03
|
11
|
O-methylglabridin
|
4.04
|
68.16
|
26
|
354.40
|
5
|
2
|
0
|
2
|
320.79
|
It is seen that phytocompounds Ginkgolide C, hispaglabridinA and Isoliquiritin have 1 violations each in Lipinski’s rule of 5 and hence can’t be considered as ligands.
Molecular Docking:
Further docking is performed with the receptors in Table 4 with the above phytocompounds (Table 4-7). Docking scores, interacting amino acids along with number of interactions are noted in Table 8-11.
Table 8
Docking of CCR5 receptor
Plant: Ginkgo biloba
|
|
COMPOUND
|
DOCKING SCORE
(Kcal/mol)
|
INTERACTING AMINO ACID
|
NO. OF INTERACTIONS
|
|
Ginkgolide A
|
-4.234
|
THR-107, GLU-336
|
2
|
|
Ginkgolide B
|
-4.342
|
ASN-311, THR- 312, THR-197, TYR-304,
|
5
|
|
Ginkgolide C
|
-4.248
|
ASP-286, THR-67, ASP-68, ARG-128
|
7
|
|
Isorhamnetin
|
-4.236
|
THR-337, TYR-39, CYS-180
|
4
|
|
Quercetin
|
-3.880
|
THR-107
|
1
|
|
Protocatechuic acid.
|
-3.840
|
ASP-68, ARG-128, ARG-142, THR-67, SER-65
|
7
|
|
Luteolin
|
-3.822
|
ASP-68, GLU-355
|
3
|
|
Plant:Uncaria tomentosa
|
|
Uncarine c
|
-4.742
|
TRY-110, GLU-335
|
2
|
|
Ajmalicine
|
-4.824
|
GLU-336
|
1
|
|
Isomitraphylline
|
-4.694
|
GLU-336, THR-107
|
2
|
|
Isopteropodine
|
-5.038
|
ASP-286
|
1
|
|
Mitraphylline
|
-4.610
|
THR-107
|
1
|
|
Isorhynchophylline
|
-5.204
|
GLU-336
|
1
|
|
Speciophylline
|
-4.586
|
GLU-336, TYR-304
|
2
|
|
Plant: Lycoris radiate
|
|
Caranine
|
-3.740
|
ARG-128, ARG-142
|
3
|
Tazettine
|
-4.428
|
TYR-110
|
1
|
Lycorine
|
-3.952
|
GLU-355
|
1
|
Lycoramine
|
-4.178
|
SER-65
|
1
|
Homolycorine
|
-4.332
|
SER-182
|
1
|
Hippeastrine
|
-3.980
|
ASP-286, LYS-64
|
2
|
galanthamine
|
-4.042
|
ASN-311
|
1
|
Plant:Glycyrrhiza glabra
|
phloretin
|
-3.852
|
THR-107
|
1
|
Rosmarinic acid
|
-4.824
|
TYR-304, ASN-311, THR-312, THR-197
|
5
|
Isocoumarin
|
-2.728
|
SER-65, THR-67
|
2
|
Cortison
|
-4.368
|
TYR-304, GLU-336, TYR-110
|
3
|
Liquiritigenin
|
-3.666
|
ASP-68, ARG-142
|
3
|
Liquiritin
|
-4.958
|
SER-65, ASP-68,GLU-355, ARG-288
|
4
|
Glabridin
|
-4.614
|
GLU-355
|
1
|
Chlorozotocin
|
-4.074
|
GLU-356,SER-65
|
3
|
hispaglabridinA
|
-5.512
|
ASP-68, ARG-285
|
2
|
Isoliquiritin
|
-5.302
|
VAL-353,ARG-288,
ARG-285,ASP-68, SER-65,LEU-289
|
8
|
O-methylglabridin
|
-4.952
|
ARG-142
|
2
|
Table 9
Docking of IFITM2 receptor
Plant: Ginkgo biloba
|
COMPOUND
|
DOCKING SCORE
(Kcal/mol)
|
INTERACTING AMINO ACID
|
NO. OF INTERACTIONS
|
Ginkgolide A
|
- 4.556
|
THR-215, VAL-145, VAL-211, VAL-131
|
4
|
Ginkgolide B
|
- 4.546
|
GLU-61
|
1
|
Ginkgolide C
|
- 4.592
|
VAL-131, THR-215
|
2
|
Isorhamnetin
|
- 4.654
|
VAL-145, THR-215
|
2
|
Quercetin
|
- 4.372
|
ALA-60
|
1
|
Protocatechuic acid
|
-4.660
|
THR-195
|
1
|
Luteolin
|
-4.378
|
VAL-145, ILE-150
|
3
|
Plant:Uncaria tomentosa
|
Uncarine C
|
- 5.064
|
VAL-131, ILE-127
|
2
|
Ajmalicine
|
- 5.336
|
ALA-16, THR-14, VAL-21, ASN-90
|
4
|
Isomitraphylline
|
- 4.876
|
GLU-58
|
1
|
Isopteropodine
|
- 4.966
|
VAL-211, THR-215
|
2
|
Mitraphylline
|
-4.686
|
THR-215
|
1
|
Isorhynchophylline
|
-5.304
|
ILE-127, VAL-211
|
2
|
Speciophylline
|
- 4.832
|
ILE-127
|
1
|
Plant: Lycoris radiate
|
Caranine
|
-4.498
|
ILE-50
|
1
|
galanthamine
|
- 4.754
|
THR-14, THR-23
|
2
|
Hippeastrine.
|
- 4.716
|
ASP-90,TYR-85, HIS-57, ALA-60
|
5
|
Homolycorine
|
-4.780
|
VAL -211
|
1
|
Lycoramine
|
-4.428
|
ASN-90, TSR-14, GLY-12
|
3
|
lycorine
|
-4.668
|
ILE-150
|
1
|
Tazettine
|
-4.620
|
TYR-85, ASN-90
|
2
|
Plant:Glycyrrhiza glabra
|
Cortison
|
-4.972
|
ILE-150, ALA-126, GLU-187
|
3
|
Glabridin
|
-5.038
|
LYS-102
|
1
|
Hispaglabridin A
|
-5.848
|
VAL-131
|
1
|
Isocoumarin
|
-2.986
|
GLY-152
|
1
|
Isoliquiritin
|
-5.744
|
THR-193, ILE-150, ASP-81, GLU-187
|
4
|
Liquiritigenin
|
-4.244
|
ASN-97
|
1
|
Liquiritin
|
-5.582
|
THR-198, ILE-88, GLY-146, VAL-145
|
3
|
O-methylglabridin
|
-5.378
|
GLY-152
|
1
|
phloretin
|
-4.852
|
TYR-85, ASP-90
|
2
|
Rosmarinicacid
|
-5.508
|
LYS-102, ASP-90
|
2
|
Chlorozotocin
|
-4.668
|
TYR-85, SER-84, ASP-90
|
5
|
Table 10
Docking of CLEC4M receptor
Plant: Ginkgo biloba
|
COMPOUND
|
DOCKING SCORE
(Kcal/mol)
|
INTERACTING AMINO ACID
|
NO. OF INTERACTIONS
|
Ginkgolide A
|
-3714
|
GLN-87, ASN-63
|
2
|
Ginkgolide B
|
-3776
|
GLN-87, GLN-10
|
3
|
Ginkgolide C
|
-3686
|
GLN-87, LYS-175
|
3
|
Isorhamnetin
|
-3420
|
ARG-51
|
1
|
Quercetin
|
-3422
|
THR-40, THR-17, THR-13, LYS-43
|
4
|
Protocatechuic acid
|
-3076
|
THR-40, LYS-20
|
2
|
Luteolin
|
-3330
|
LYS-176
|
1
|
Plant:Uncaria tomentosa
|
Uncarine C
|
-4182
|
ASN-63
|
1
|
Ajmalicine
|
-4178
|
GLN-87
|
1
|
Isomitraphylline
|
-4390
|
THR-58, ASP-56
|
1
|
Isopteropodine
|
-4178
|
GLN-87
|
1
|
Mitraphylline
|
-4086
|
GLM-84
|
1
|
Isorhynchophylline
|
-4332
|
ASN-63
|
1
|
Speciophylline
|
-3936
|
GLN-10,LYS-175, ASN-63
|
4
|
Plant: Lycoris radiate
|
Caranine
|
-3340
|
ASN-69,MET-67.
|
2
|
galanthamine
|
-3602
|
THR-17
|
1
|
Hippeastrine.
|
-3484
|
LYS-175
|
1
|
Homolycorine
|
-3758
|
LYS-20
|
1
|
Lycoramine
|
-3662
|
LYS-20, THR 40
|
2
|
lycorine
|
-3458
|
MET-67, THR-58
|
2
|
Tazettine
|
-3770
|
LYS-92
|
1
|
Plant:Glycyrrhiza glabra
|
Cortison
|
-3714
|
ASN-63, GLN-87, TYR-13
|
3
|
Glabridin
|
-3906
|
LYS-176, GLU-5, LYS-8
|
3
|
HispaglabridinA
|
-4884
|
ASN-63
|
1
|
Isocoumarin
|
-2296
|
THR-40
|
1
|
Isoliquiritin
|
-4250
|
CYS-180, ARG-182
|
2
|
Liquiritigenin
|
-3310
|
LYS-8,LYS-176,PHE-181,ALA-178
|
4
|
Liquiritin
|
-4408
|
GLN-87, ARG-85
|
2
|
O-methylglabridin
|
-4268
|
ARG-109, THR-58
|
2
|
phloretin
|
-3390
|
GLU-5, ARG-85,VAL-84
|
3
|
Rosmarinicacid
|
-4488
|
LYS-176
|
1
|
Chlorozotocin
|
-3532
|
LYS-176, GLU-5, LYS-8
|
3
|
Table 11
Docking of IFR3 receptor
Plant: Ginkgo biloba
|
NO. OF INTERACTIONS
|
NO. OF INTERACTIONS
|
NO. OF INTERACTIONS
|
NO. OF INTERACTIONS
|
Ginkgolide A
|
-4966
|
PRO-153, SER-152, HIS-151, ARG-25, ARG-193
|
6
|
Ginkgolide B
|
-5054
|
SER-152, GLU-110, ARG-193, SER-152, GLY-26, ARG-25
|
6
|
Ginkgolide C
|
-4842
|
TYR-155, GLU-111, GLY-26, VAL-172, ARG-25,
|
6
|
Isorhamnetin
|
-4672
|
ARG-25, ARG-27, SER-152, LEU-200
|
4
|
Quercetin
|
-4388
|
LEU-200, ARG-193, ARG-27, ARG-25, TYR-155, THR-156
|
6
|
Protocatechuic acid
|
-4052
|
GLY-26, TYR-155, SER-152 ARG-193
|
4
|
Luteolin
|
-4300
|
ARG-27, LYS-173, GLU-111, LEU-200, ARG-25
|
6
|
Plant: Uncaria tomentosa
|
Uncarine c
|
-5362
|
GLU-110, SER-152, LEU-200, LYS-173, ARG-25
|
5
|
Ajmalicine
|
-5208
|
GLU-111, SER-152, GLU-110, TYR-155
|
4
|
Isomitraphylline
|
-5246
|
SER-152, GLU-110, TYR-155, ARG-25
|
4
|
Isopteropodine
|
-4892
|
ARG-25, ARG-193, GLU-110
|
3
|
Mitraphylline
|
-5292
|
LYS-152, SER-152
|
2
|
Isorhynchophylline
|
-5338
|
ARG-25, GLU-110,TYR-155, ARG-193
|
5
|
Speciophylline
|
-5068
|
LEU-200,GLU-110, ARG-25
|
3
|
Plant: Lycoris radiate
|
Caranine
|
-4180
|
ARG-25
|
1
|
galanthamine
|
-4632
|
LYS-173, ARG-25
|
2
|
Hippeastrine.
|
-4644
|
SER-152
|
1
|
Homolycorine
|
-5034
|
SER-152, GLU-110,LYS-173,
|
1
|
Lycoramine
|
-4508
|
LEU-200, GLU 110
|
2
|
lycorine
|
-4418
|
SER-152, VAL-172, ARG-25, GLU-110
|
4
|
Tazettine
|
-5380
|
SER-152, ARG-25
|
2
|
Plant: Glycyrrhiza glabra
|
Cortison
|
-5186
|
GLY-150, TYR-155, ARG-25, ARG-27, GLU-111
|
6
|
Glabridin
|
-5092
|
ARG-193, SER-152, LEU-200, ARG-25
|
2
|
Hispaglabridin A
|
-6154
|
ARG-25
|
1
|
Isocoumarin
|
-2978
|
LYS-173, GLU-110
|
2
|
Isoliquiritin
|
-5440
|
ARG-154,ARG-27, ARG-193, TYR-155
|
4
|
Liquiritigenin
|
-4388
|
GLY-26, LYS-173, GLY-150,LEU-200, TYR-155
|
5
|
Liquiritin
|
-5706
|
HIS-151, GLU-110, TYR-155, ARG-25,
|
6
|
O-methylglabridin
|
-5594
|
TYR-155, ARG-193
|
2
|
phloretin
|
-4576
|
LEU-200, GLU-111, ARG-193, ASP-67, ARF-25, SER-152
|
5
|
Rosmarinicacid
|
-5214
|
ASP-67, ARG-193, SER-198, LEU-200,LYS-173, GLU-111
|
6
|
Chlorozotocin
|
-4648
|
ARG-25, TYR-155, SER-152, ASP-67
|
4
|
As per docking studies it is seen that phytocompounds Ginkgolide A, Ginkgolide B, Luteolin and Protocatechuic acid from Ginkgo biloba and Liquiritin, Cortison and Chlorozotocin from Glycyrrhiza glabra have good interactions with the West Nile fever gene receptors.