Id |
Subject |
Object |
Predicate |
Lexical cue |
T396 |
0-4 |
Sentence |
denotes |
3.3. |
T397 |
6-86 |
Sentence |
denotes |
Docking studies of WS phytoconstituents with respect to selected target proteins |
T398 |
87-225 |
Sentence |
denotes |
Docking studies of the selected WS phytoconstituents were carried out with human ACE2 receptor, SARS-CoV and SARS-CoV-2 specific proteins. |
T399 |
226-463 |
Sentence |
denotes |
The catalytically active sites of SARS-CoV-2 specific proteins were targeted in order to obtain the binding energy involved in the complex formation and to discover the molecular mechanisms responsible for specific inhibition of targets. |
T400 |
464-711 |
Sentence |
denotes |
Tables 5–11 summarize the predicted binding energies and dissociation constants (Kd) of WS phytoconstituents with respect to specific human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases viz. |
T401 |
712-731 |
Sentence |
denotes |
3CL-pro and PL-pro. |
T402 |
732-947 |
Sentence |
denotes |
The binding sites of the WS phytoconstituents on the selected viral target proteins as well as the interacting amino acids were predicted to be almost the same by the three molecular docking softwares (Tables 5–11). |
T403 |
948-1063 |
Sentence |
denotes |
The common interacting amino acids between the three softwares have been written in italicized form in Tables 5–11. |
T404 |
1064-1195 |
Sentence |
denotes |
As is evident from Tables 5–11, most of the WS phytoconstituents exhibited potent binding kinetics to the above-mentioned proteins. |
T405 |
1196-1509 |
Sentence |
denotes |
Docking analyses using AutoDock 4.0/ADT version 4.2.6 program revealed that the binding affinities of the WS phytoconstituents for the human ACE2 receptor decreased in the order withanolide B > withanolide A > withanolide E > viscosalactone B > withaferin A > anaferine > withanolide D > withanone > withasomnine. |
T406 |
1510-1616 |
Sentence |
denotes |
Withanolide B exhibited a 1000× stronger binding to human ACE2 receptor (Table 5; BE: −10.21 kcal/mol, Kd: |
T407 |
1617-1709 |
Sentence |
denotes |
32.78 nM) as compared to standard reference drugs, arbidol (Table 5; BE: −6.69 kcal/mol, Kd: |
T408 |
1710-1766 |
Sentence |
denotes |
12.47 µM) and losartan (Table 5; BE: –6.72 kcal/mol, Kd: |
T409 |
1767-1777 |
Sentence |
denotes |
11.86 µM). |
T410 |
1778-1892 |
Sentence |
denotes |
Withanolide B also exhibited potent binding to papain like protease of SARS-CoV-2 (Table 8; BE −10.3 kcal/mol, Kd: |
T411 |
1893-1963 |
Sentence |
denotes |
28.32 nM) as compared to procainamide (Table 8; BE −5.03 kcal/mol, Kd: |
T412 |
1964-2022 |
Sentence |
denotes |
206.96 µM) and cinacalcet (Table 8; BE −6.44 kcal/mol, Kd: |
T413 |
2023-2033 |
Sentence |
denotes |
19.17 µM). |
T414 |
2034-2042 |
Sentence |
denotes |
Table 5. |
T415 |
2044-2118 |
Sentence |
denotes |
Binding energies of WS phytoconstituents with human ACE2 receptor (PDB ID: |
T416 |
2119-2207 |
Sentence |
denotes |
1O8A) in comparison to the FDA approved standard reference drugs (Arbidol and Losartan). |
T417 |
2208-2256 |
Sentence |
denotes |
AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T418 |
2257-2259 |
Sentence |
denotes |
S. |
T419 |
2260-2263 |
Sentence |
denotes |
No. |
T420 |
2265-2418 |
Sentence |
denotes |
Ligands BE (kcal/mol) K d Interacting amino acids BE(kcal/mol) K d Interacting amino acids TE(kcal/mol) VDW HB EI Interacting amino acids |
T421 |
2419-2421 |
Sentence |
denotes |
1. |
T422 |
2423-2903 |
Sentence |
denotes |
Withaferin A –8.44 647.61 nM Glu123, Met223, Trp220, Pro519, Arg522, Ser517, Val518, Glu411, His410, Ser355, Ala356, His387, Phe391, Glu403 –10.4 23.67 nM His353, Val518, His513, Tyr523, Glu411, Arg522, Phe512, Ala356, Ser355, Ser516, Glu143, Asn70, Asn66, Tyr69, Leu140, Leu139, Leu81, Asn85, Tyr62, Asn136, Arg124 –111.33 –90.07 –21.26 0 Ser284, Tyr287, Val291, Asp288, Asn285, Glu376, Leu375, Asn374, Thr302, Thr301, Asp300, Met299, Ser298, Pro297, Pro294, Ala296 |
T423 |
2904-2906 |
Sentence |
denotes |
2. |
T424 |
2908-3320 |
Sentence |
denotes |
Withanolide A –10.13 37.44 nM Asp453, Thr282, Gln281, Phe457, Glu376, Val379, Val380, Asp415, His383, Glu384, Ala354, His353, His387, Glu411, His513, Phe512, Tyr523 –10.6 15.57 nM His410, Ala353, His387, Trp357, Phe391, Asn66, Asn70, Ser516, Glu143, Phe512, Val518, His353, Ser355, His513, Tyr523, Glu411, Arg522 –98.26 –78.36 –19.90 0 Leu375, Lys449, Tyr287, Ser298, Met299, Asp300, Thr301, Thr302 |
T425 |
3321-3323 |
Sentence |
denotes |
3. |
T426 |
3325-3805 |
Sentence |
denotes |
Withanolide B –10.21 32.78 nM Phe391, His387, Ala356, His383, Ser355, Ala354, His353, Glu403, Gly404, His410, Glu411, Pro407, Tyr523, Arg522, Phe512, His513, Met223 –10.7 10.60 nM Asn85, Tyr62, Arg124, Asn66, Phe512, His353, Val518, His513, Tyr523, Arg522, Glu411, Leu81, Leu140, Leu139, Tyr69, Glu143, Asn70, Ser516, Ser355, Ala356, His387 –97.61 –86.31 –11.29 0 Thr226, Glu225, Pro227, Tyr224, Leu229, Ser222, Arg221, Asp218, Tyr213, Asn211, Asp121, Gln120, Lys117 |
T427 |
3806-3808 |
Sentence |
denotes |
4. |
T428 |
3810-4263 |
Sentence |
denotes |
Withanolide D –8.23 934.88 nM Phe391, Ala356, Ser355, His387, Glu384, Ala354, His353, Glu411, Tyr523, Val518, His383, Val380 –11.3 600 pM Glu411, Tyr523, Arg522, His410, Phe391, Ala356, His387, Asn66, Asn70, Tyr69, Trp357, Glu143, Val351, Ser516, Phe512, His353,Val518, Ser355 –101.56 –82.00 –19.56 0 Arg124, Leu140, Leu81, Glu143, Asn66, Asn70, Tyr69, His353, Ala354, Ser355, Ala356, Glu384, His387, Glu411, Tyr523, Val518, His513, Phe512 |
T429 |
4264-4266 |
Sentence |
denotes |
5. |
T430 |
4268-4715 |
Sentence |
denotes |
Withanolide E –9.75 71.2 nM Phe391, His410, His387, Glu411, Arg522, Tyr523, Val518, His513, Phe512, His353, Ala354, Ser355, Glu384, Ala356, Lys368, Asn70 –10.6 15.45 nM Arg124, Leu140, Leu139, Leu81, Asn70, Tyr69, Glu143, Ser516, Val351, Trp357, Phe512, His353, Ser355, Ala356, Glu384, His387, Phe391, Val518, Tyr62, Asn66 –104.39 –90.97 –13.41 0 Glu239, Arg235, Leu236, Asp232, Ser228, Thr226, Pro575, Trp574, Pro585, Asn586, Met587 |
T431 |
4716-4718 |
Sentence |
denotes |
6. |
T432 |
4720-5129 |
Sentence |
denotes |
Withanone –8.12 1.12 µM Ser422, Phe527, Lys454, Tyr523, Val379, His383, Glu384, Val380, His513, Gln281, Thr282, Ser284, Phe457, Asp453 –10.2 31.56 nM Lys449, Val291, Pro297, Ser298, Asp300, Met299, Ser284, Asn285, Asn374, Glu376, Thr302, Leu375, Thr301, Tyr287, Asp288 –100.15 –79.22 –20.92 0 Asn374, Leu375, Thr302, Thr301, Asp300, Met299, Ser298, Pro297, Ala296, Pro294, Val291, Tyr287, Asn285 |
T433 |
5130-5132 |
Sentence |
denotes |
7. |
T434 |
5134-5673 |
Sentence |
denotes |
Viscosalactone B –8.83 339.1 nM Ala356, His387, Ser355, Glu384, Ala354, His353, His513, Phe512, Tyr523, Thr282, Asp453, Ser284, Glu376, Val379, Val380, His383, Glu411 –11.1 760 pM Tyr62, Asn85, Asn136, Leu81, Glu143, Leu139, Leu140, Asn66,Asn70, Phe512, Ala356, Ser355, Ala354, His353, Tyr523, His383, His387, Glu411, Arg522, Val518, Arg124 –119.88 –92.25 –27.63 0 Tyr62, Leu81,Asn136, Asn66, Tyr69, Leu139, Leu140, Glu143, Ser516, Asn70, His513, His353, Ala354, Tyr523, Ser355, Ala356, Trp357, His387, Glu411, Glu384, His383 |
T435 |
5674-5676 |
Sentence |
denotes |
8. |
T436 |
5678-6029 |
Sentence |
denotes |
Anaferine –8.25 890.86 nM Glu411, Tyr523, His383, His387, Glu384, Val380, Ala356, Ser355, Ala354, His353 –6.7 12.50 µM His383, His387, Ala354, Glu384, Ser355, Ala356, Val518, His513, Phe512, His353, Tyr523, Tyr520, Gln281, Phe457, Phe527 –77.85 –74.35 –3.5 0 Phe570, Met223, Asn406, Glu403, Gly404, Pro407, His410, Phe391, Glu411, His387 |
T437 |
6030-6032 |
Sentence |
denotes |
9. |
T438 |
6034-6337 |
Sentence |
denotes |
Withasomnine –4.99 218.08 µM Tyr523, His513, Val380, His383, Glu384, His387, Ala356, Ser355, Ala354, His353 –6.7 12.59 µM Phe291, Tyr394, His410, Arg522, Gly404, Pro407, Glu403, Met223, Phe570, Asn406 –74.24 –64.10 –10.14 0 Leu122, Thr92, Ala125, Arg124, Ala89, Ile88, Asn85, Asn136, Trp59 |
T439 |
6338-6341 |
Sentence |
denotes |
10. |
T440 |
6343-6786 |
Sentence |
denotes |
Arbidol –6.69 12.47 µM Ala354, His353, Glu162, Lys511, Trp279, Gln281, Thr282, Phe457, Asp453, Tyr523, Lys454, Phe527, Asp415, His383, Val380, Glu384 –8.3 880.23 nM Phe570, Met223, Asn406, Gly404, Glu403, Arg402, Tyr394, Tyr360, Phe391, Asp358, Trp357, Ala356,His387, His410, Glu411, Arg522, Pro407 –86.22 –73.55 –12.67 0 Phe391, His410, Glu411, His387, Trp357, Ala356, Ser355, Ala354, His353, Asn66, Ala63, Tyr62, Val518, Tyr523 |
T441 |
6787-6790 |
Sentence |
denotes |
11. |
T442 |
6792-7206 |
Sentence |
denotes |
Losartan –6.72 11.86 µM Asn406, Met223, Arg522, Pro407, Gly404, Glu403, His410, Glu411, Tyr523, Phe391, His387, Ala356, Val518 –9.4 129.59 nM Met223, Pro519, Arg522, His410, His387, Tyr523, Glu411, Ser355, Val518, Ala356, Asp358, Tyr360, Phe391, Gly404, Glu403, Asn406, Pro407 –101.28 –85.24 –16.04 0 Asp121, Leu122, Thr92, Trp220, Glu123, Arg124, Ala89, Ile88, Pro519, Tyr62, Ser517, Tyr135, Ile204 |
T443 |
7207-7215 |
Sentence |
denotes |
Table 6. |
T444 |
7217-7299 |
Sentence |
denotes |
Binding energies of WS phytoconstituents with SARS-CoV spike glycoprotein (PDB ID: |
T445 |
7300-7398 |
Sentence |
denotes |
5WRG) in comparison to the FDA approved standard reference drugs (Arbidol and Hydroxychloroquine). |
T446 |
7399-7447 |
Sentence |
denotes |
AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T447 |
7448-7450 |
Sentence |
denotes |
S. |
T448 |
7451-7454 |
Sentence |
denotes |
No. |
T449 |
7456-7609 |
Sentence |
denotes |
Ligands BE (kcal/mol) K d Interacting amino acids BE(kcal/mol) K d Interacting amino acids TE(kcal/mol) VDW HB EI Interacting amino acids |
T450 |
7610-7612 |
Sentence |
denotes |
1. |
T451 |
7614-8012 |
Sentence |
denotes |
Withaferin A –8.39 702.21 nM Ile979, Leu983, Thr980, Gly981, Gln984, Tyr738, Leu983, Gln984, Thr980 –10.3 28.30 nM Lys715, Ala753, Ala754, Asp757, Arg761, Leu846, Arg758, Pro651, Ile652, Leu843, Leu597, Gln599, Ala633, Val581, Tyr300, Thr302 –104.25 –83.69 –20.56 0 Arg453, Glu452, Asp454, Ser456, Arg449, Arg441, Val458, Pro459, Arg444, His445, Phe460, Pro466, Gly464, Ser461, Lys465 |
T452 |
8013-8015 |
Sentence |
denotes |
2. |
T453 |
8017-8373 |
Sentence |
denotes |
Withanolide A –9.78 67.23 nM Gln984,Leu983, Thr980, Gly981, Arg977, Phe952, Tyr738 –10.5 19.50 nM Ile299, Ala754, Ser750, Thr302, Ala753, Val581, Leu843, Gln599, Ile652, Arg758, Lys715, Gly653, Asp757, Tyr300, Arg761, Pro651, Leu846 –97.67 –85.32 –12.35 0 Ile652, Pro651, Thr302, Tyr300, Ile299, Gln301, Ser750, Ala754, Arg747, Gly751, Lys715 |
T454 |
8374-8376 |
Sentence |
denotes |
3. |
T455 |
8378-8718 |
Sentence |
denotes |
Withanolide B –9.4 129.59 nM Gln984, Thr980, Leu983, Gly981, Arg977, Phe952, Tyr738, Asp976 –10.4 23.67 nM Ser950, Asn951, Gly981, Arg977,Thr980, Asp976, Asp976, Phe952,Gln984, Leu983, Gln947, Phe741, Ser985, Tyr738 –100.62 –94.31 –6.32 0 Lys715, Asp757, Ala753, Arg761, Arg758, Ala754, Leu846, Gly653, Ile652, Pro651, Tyr300 |
T456 |
8719-8721 |
Sentence |
denotes |
4. |
T457 |
8723-9103 |
Sentence |
denotes |
Withanolide D –9.1 212.78 nM Thr980, Gly981, Leu983, Tyr738, Phe952, Gln984, Asp976, Ile979 –10.7 11.45 nM Ile299, Ala754, Pro651, Arg758, Arg761, Asp757, Leu846, Leu597, Lys715, Val581, Ile652, Ala633, Gln599, Leu843, Tyr300, Ser750, Ala753, Thr302 –103.3 –84.53 –18.77 0 Ala926,Leu927, Ser924, Gly928, Thr925, Gln931, Asn935, Lys297, Asp296, Ile295, Glu294, Val290 |
T458 |
9104-9106 |
Sentence |
denotes |
5. |
T459 |
9108-9485 |
Sentence |
denotes |
Withanolide E –7.13 5.93 µM Thr980, Gly981, Gln984, Arg977, Tyr738, Leu983 –9.5 99.21 nM Lys715, Ala753, Ser750, Pro844, Thr302, Leu843, Ala633,Gln599, Ile652, Leu597, Val581, Ile299, Pro651, Ile650, Tyr300, Ala754 –99.34 –93.84 –5.49 0 Leu597,Ala633, Gln599, Ile652, Val581, Pro651, Thr302, Ile650, Tyr300, Ile299, Pro844, Leu843, Lys715, Ser750, Ala753, Ala754 |
T460 |
9486-9488 |
Sentence |
denotes |
6. |
T461 |
9490-9834 |
Sentence |
denotes |
Withanone –6.49 17.46 µM Thr980, Gly981, Gln984, Leu983, Phe741,Tyr738 –9.5 99.56 nM Arg747, Gly751, Ala754, Pro651, Ile652, Lys715, Gln599, Val581, Tyr200, Leu843, Ala753, Thr302, Ser750, Ile299, Gln939, Gln301 –104.09 –85.03 –19.07 0 Leu810, Ala938, Asn942, Lys946, Thr943, Gln744, Arg747, Thr743, Ser289, Gln301, Val290, Lys291 |
T462 |
9835-9837 |
Sentence |
denotes |
7. |
T463 |
9839-10263 |
Sentence |
denotes |
Viscosalactone B –7.6 2.69 µM Gln987, Gln984, Leu983, Thr980, Asp976, Phe952, Gly981, Gln984, Thr988 –10.2 32.60 nM Leu994, Ile995, Glu999, Ala998, Ile752, Arg1001, Ala997, Glu755, Gln936, Asp932, Ile299, Asp296, Tyr300, Gln301, Gln939, Arg747, Ala748, Gly751, Arg996 –121.82 –89.39 –32.43 0 Arg563, Arg315, Phe551, Gln550, Asn530, Gly531, Asn505, Leu504, Leu503, Ser380, Phe379, Cys378, Arg965, Asn530, Gly551 |
T464 |
10264-10266 |
Sentence |
denotes |
8. |
T465 |
10268-10602 |
Sentence |
denotes |
Anaferine –6.94 8.16 µM Gln947, Phe741, Ser985, Gln984, Gly981, Tyr738, Phe952, Leu983, Thr980, Ile979, Asp976 –7.0 6.40 µM Arg747, Thr943, Gln744, Thr988, Gln987, Phe741, Gln947, Ser985, Tyr989, Leu944, Ala940, Gln992 –84.12 –69.13 –14.99 0 Arg965, Leu374, Lys373, Tyr352, Cys378, Leu503, Phe501, Met417, Val369, Ser370 |
T466 |
10603-10605 |
Sentence |
denotes |
9. |
T467 |
10607-10920 |
Sentence |
denotes |
Withasomnine –5.87 49.69 µM Gln947, Phe741, Ser985, Gln984, Gly981, Leu983, Phe952, Asn951, Tyr738, Ser950 –7.1 6.25 µM Leu963, Ser728, Cys725, Val958, Leu948, Phe558, Asp557, Phe837, Asn960, Thr535, Thr533, Asp727, Leu959 –80.03 –72.43 –7.60 0 Cys278, Phe262, Met263, Val276, Cys288, Lys287, Ser292 |
T468 |
10921-10924 |
Sentence |
denotes |
10. |
T469 |
10926-10992 |
Sentence |
denotes |
Arbidol –4.91 251.65 µM Phe952, Gln947, Gly739, Phe741, Tyr738. |
T470 |
10993-11246 |
Sentence |
denotes |
Gly981, Arg977, Thr980, Asp976, Thr980, Leu983, Gln984 –7.7 2.20 µM Ala754, Ser750, Asn746, Arg747, Thr302, Gln599, Gln301, Val581, Tyr300 –83.02 –78.02 –5 0 Leu859, Pro1035, Phe1034, Ser1033, Cys1014, Val1015, Gln883, Leu1016, Pro879, Gly862 |
T471 |
11247-11250 |
Sentence |
denotes |
11. |
T472 |
11252-11583 |
Sentence |
denotes |
Hydroxychloroquine –5.25 142.18 µM Gln984, Leu983, Thr980, Ile979,Ser985, Gly981, Phe741, Gln947, Tyr738, Phe952 –7.0 7.0 µM Ala753, Ser750, Pro651, Lys715, Leu843, Gly653, Ile652, Val581, Tyr300, Thr302, Gln599, Leu597, Ile299, Ala754 –76.22 –68.13 –8.09 0 Lys1027, Gly1026, Val1022, Ser1012, Val1015, Gln766, Lys768 |
T473 |
11584-11592 |
Sentence |
denotes |
Table 7. |
T474 |
11594-11772 |
Sentence |
denotes |
Binding energies of WS phytoconstituents with SARS-CoV-2 spike glycoprotein (PDB ID:6VXX) in comparison to FDA approved standard reference drugs (Arbidol and Hydroxychloroquine). |
T475 |
11773-11824 |
Sentence |
denotes |
AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T476 |
11825-11827 |
Sentence |
denotes |
S. |
T477 |
11828-11831 |
Sentence |
denotes |
No. |
T478 |
11833-11983 |
Sentence |
denotes |
Ligands BE (kcal/mol) K d Interacting amino acids BE(kcal/mol) K d Interacting amino acids TE(kcal/mol) VDW HB EI Interacting amino acids |
T479 |
11984-11986 |
Sentence |
denotes |
1. |
T480 |
11988-12297 |
Sentence |
denotes |
Withaferin A –6.11 33.39 µM Leu303, Tyr313, Thr302, Gln314, Thr315, Ser316, Asn317, Arg319 –8.6 447.56 nM Gln218, Phe59, Gly219, Phe220, Thr33, Asp287, Phe58, Val289, Ser297, Lys300, Asp294, Leu296, Asn606, Leu293 –84.45 –66.52 17.93 0 Thr430, Asp428, Phe515, Ser514, Glu516, Tyr396, Arg355, Phe464 |
T481 |
12298-12300 |
Sentence |
denotes |
2. |
T482 |
12302-12627 |
Sentence |
denotes |
Withanolide A –7.18 5.48 µM Glu309, Tyr313, Thr302, Leu303, Lys304, Gln957 –8.4 650.76 nM Leu977, Cys743, Val976, Asn978, Leu966, Ser975, Ser967, Arg44, Ser45, Val47, Asn856, Arg1000, Tyr741, Ile742 –83.67 –61.91 –21.76 0 Arg273, Pro272, Cys291, Thr274, Cys301, Gln52, Lys304, Ser50, Thr301, Thr315, Ala292, Glu298 |
T483 |
12628-12630 |
Sentence |
denotes |
3. |
T484 |
12632-12951 |
Sentence |
denotes |
Withanolide B –6.81 10.26 µM Gln31, Tyr313, Thr302, Leu303, Lys304, Gln957, Asn960, Lys964 –8.0 771.67 nM Arg319, Thr572, Thr573, Asp571, Arg567, Leu546, Thr547, Gly548, Phe541, Thr549, Pro589, Cys590, Phe592, Arg319 –86.89 –78.89 –7.9 0 Asn556, Ile584, Leu582, Arg577, Lys557, Lys558, Phe559, Leu560, Pro561 |
T485 |
12952-12954 |
Sentence |
denotes |
4. |
T486 |
12956-13068 |
Sentence |
denotes |
Withanolide D –6.9 8.68 µM Gln957, Thr961, Lys964, Gln965, Ser967, Ser968, Leu303, Lys304, Thr302 –8.7 398. |
T487 |
13069-13325 |
Sentence |
denotes |
84 nM Val976, Arg1000, Phe855, Ser975, Lys854, Val963, Asn856, Ser967, Leu966, Asn978, Leu977, Asp745, Met740, Gly744, Tyr741 –82.91 –69.68 –13.23 0 Gln954, Ala958, Thr961, Leu962, Arg1014, Glu1017, Ile1013, Gln1010, Tyr1007, Thr1006, Ser1003, Gln965 |
T488 |
13326-13328 |
Sentence |
denotes |
5. |
T489 |
13330-13598 |
Sentence |
denotes |
Withanolide E –6.94 8.17 µM Gln957, Lys964, Lys304, Leu303, Thr302 –8.0 771.57 nM Asn30, Phe59, Thr33, Phe58, Phe306, Val289, Ala288, Lys300, Ser297, Leu296, Leu293, Asp294 –91.24 –82.26 –8.98 0 Glu340, Gly339, Phe338, Cys336, Ala363, Asp364, Val362, Leu335 |
T490 |
13599-13601 |
Sentence |
denotes |
6. |
T491 |
13603-13889 |
Sentence |
denotes |
Withanone –7.15 5.75 µM Gln309, Ser305, Leu303, Lys304, Thr302, Lys964, Gln957 –8.0 771.87 nM Asn978, Val963, Lys964, Ser967, Asn856, Ser975, Val976, Leu966, Tyr741, Leu977, Arg1000, Gly744 –84.14 –69.21 –14.92 0 Pro793, Pro792, Thr791, Lys790, Pro897, Thr883, Ile896, Gln895 |
T492 |
13890-13892 |
Sentence |
denotes |
7. |
T493 |
13894-14221 |
Sentence |
denotes |
Viscosalactone B –6.02 38.89 µM Gln957, Ser305, Lys304, Leu303, Thr302, Thr315, Gln31, Ser316, Asn317 –8.2 935.88 nM Asn856, Gly744, Arg1000, Val976, Ser975, Ser967, Leu966, Asn978, Leu977 –98.52 –80.77 –17.75 0 Phe86, Asn87, Ile235, Asp88, Asn234, Pro272, Ile233, Leu54, Asn196, Asp53, Gln52, Ile197, Gly199, Asp198 |
T494 |
14222-14224 |
Sentence |
denotes |
8. |
T495 |
14226-14528 |
Sentence |
denotes |
Anaferine –3.86 1.47 mM Tyr313, Glu309, Leu303, Lys304, Gln957 –5.0 213.05 µM Ser967, Ser975, Val976, Leu977, Arg1000, Asn978, Gly744, Asp745, Met740, Phe855, Tyr741, Leu966, Asn856, Val963, Lys964 –72.56 –58.62 –13.94 0 Lys933, Ser929, Ile934, Ala930, Gln926, Thr719, Ser721, Ile720, Val722 |
T496 |
14529-14531 |
Sentence |
denotes |
9. |
T497 |
14533-14832 |
Sentence |
denotes |
Withasomnine –4.51 494.91 µM Ser316, Thr315, Glu298, Cys291, Thr302, Cys301, Thr274, Lys304, Ser50 –6.2 29.91 µM Ser1003, Leu962, Tyr1007, Gln957, Arg1014, Gln1010, Ala958, Thr1006, Gln965, Thr961 –73.49 –65.71 –7.78 0 Glu1111, Gln1113, Thr1105, Gln1106, Val1104, Thr912, Asn1119, Glu1092 |
T498 |
14833-14836 |
Sentence |
denotes |
10. |
T499 |
14838-15149 |
Sentence |
denotes |
Arbidol –3.14 4.99 mM Glu309, Tyr313, Gln314, Leu303, Thr302, Gln957, Thr961, Lys964 –5.8 56.89 µM Phe59, Thr33, Phe220, Thr286, Asp287, Ala288, Val289, Asp290, Leu293, Asp294, Leu296, Ser297, Lys300 –78.93 –72.29 –6.64 0 Thr618, Glu619, Gln644, Asn616, Val615, Asp614, Phe592, Cys590, Pro589, Thr589 |
T500 |
15150-15153 |
Sentence |
denotes |
11. |
T501 |
15155-15444 |
Sentence |
denotes |
Hydroxychloroquine –2.48 15.11 mM Ser50, Cys301, Glu298, Thr302, Thr315, Ser316 –6.1 35.2 µM Asp294, Leu296, Leu293, Ser297, Lys300, Val289, Asp287, Phe306, Thr33, Asn606, Thr602 –72.42 –62.92 –9.5 0 Val722, Thr724, Ile726, Ile934, Ser937, Leu938, Thr941, Ala944, Ser943, Ile726 |
T502 |
15445-15453 |
Sentence |
denotes |
Table 8. |
T503 |
15455-15544 |
Sentence |
denotes |
Binding energies of WS phytoconstituents with papain like protease of SARS-CoV-2 (PDB ID: |
T504 |
15545-15640 |
Sentence |
denotes |
6W9C) in comparison to the FDA approved standard reference drugs (Procainamide and Cinacalcet). |
T505 |
15641-15692 |
Sentence |
denotes |
AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T506 |
15693-15695 |
Sentence |
denotes |
S. |
T507 |
15696-15699 |
Sentence |
denotes |
No. |
T508 |
15701-15851 |
Sentence |
denotes |
Ligands BE (kcal/mol) K d Interacting amino acids BE(kcal/mol) K d Interacting amino acids TE(kcal/mol) VDW HB EI Interacting amino acids |
T509 |
15852-15854 |
Sentence |
denotes |
1. |
T510 |
15856-16153 |
Sentence |
denotes |
Withaferin A –8.74 393.84 nM Asn109, Leu162, Gly160, Gln269, Glu161, Val159, His89, Thr158 –9.8 61.88 nM His89, Val159, Gly160, Glu161,Leu162, Gln269, Asn109, Thr158 –101.80 –86.23 –15.57 0 Trp106, Ala107, Asn267, Asp108, Leu162, Gly163, Lys157, Asp164, Glu167, Tyr264, Pro248, Pro247 |
T511 |
16154-16156 |
Sentence |
denotes |
2. |
T512 |
16158-16484 |
Sentence |
denotes |
Withanolide A –10.19 34.04 nM Gln269, Asn109, Leu162, Glu161, Gly160, Val159, Thr158 –10.2 32.78 nM Asp286, Asn267, Asp164, Tyr264, Tyr273, Pro248, Gly163, Leu162, Lys157, Asp108, Ala107, Trp106, Gly266, Ala288, Lys105, Tyr268, Leu289 –103.61 –84.71 –18.90 0 Asn109, Val159, Thr158, Glu161, Gly160, Gln269, Leu162 |
T513 |
16485-16487 |
Sentence |
denotes |
3. |
T514 |
16489-16767 |
Sentence |
denotes |
Withanolide B –10.3 28.32 nM Gln269, Asn109, Leu162, Glu161, Gly160, Val159, His89, Thr158 –10.4 22.51 nM His89, Thr158, Gly160, Asn109,Gln269, Leu162, Val159 –104.57 –96.14 –8.43 0 Thr158, Leu162, Glu161, Gly160, His89, Asp108, Ser85, Ala86, Gly160, Val159, Asn109 |
T515 |
16768-16770 |
Sentence |
denotes |
4. |
T516 |
16772-17078 |
Sentence |
denotes |
Withanolide D –9.56 98.21 nM Gly160, Glu161, Asn109, Gln269, Cys270, Leu162, Cys160, Val159, Thr158, His89 –10.1 38.9 nM Thr158, His89, Glu161, Gly160, Asn109, Gln269, Leu162, Val159 –99.07 –91.72 –7.35 0 Pro59, Ala68, Arg65, Phe69, Thr74, Thr75, Pro77, Ile44, Lys45, Pro46, Met23, His47, Asn48 |
T517 |
17079-17081 |
Sentence |
denotes |
5. |
T518 |
17083-17351 |
Sentence |
denotes |
Withanolide E –9.05 231.88 nM Asn109, Gln269, Leu162, Gly160, Asp108, Glu161, His89 –10.6 15.57 nM Asp108, Thr158, Glu161, Val159, His89, Gly160, Leu162, Asn109, Gln269 –107.44 –76.48 –30.96 0 Thr158, Asn109, Gly160, Glu161, Leu162, Asp108, Val159, His89 |
T519 |
17352-17354 |
Sentence |
denotes |
6. |
T520 |
17356-17662 |
Sentence |
denotes |
Withanone –9.09 218.4 nM Val159, Gly160, Glu161, Asn109, Leu162, Gln269, Gln269 –10.1 38.83 nM Trp106, Glu167, Ala107, Trp93, Lys92, His89, Asp108, Lys157, Asp164, Tyr264, Gly163, Tyr273, Val165, Thr301, Pro248 –109.36 –87.06 –22.31 0 Asn109, Thr158, Gly160, Gln269,Glu161, Leu162, Val159,His89 |
T521 |
17663-17665 |
Sentence |
denotes |
7. |
T522 |
17667-18040 |
Sentence |
denotes |
Viscosalactone B –9.02 243.41 nM Ser85, Ala86, His89, Va159, Gly160, Asp108, Asn109, Gln269, Leu162,Glu161 –9.7 70.23 nM Lys92, His89, Val159, Trp93, Asp108, Leu162, Gly163, Tyr273, Tyr264, Pro248, Pro247, Thr301, Asp164, Lys105, Glu167, Trp106, Ala107, Glu161, Lys157 –102.08 –86.12 –15.96 0 Leu162, Glu161, Gly160, Val159, Thr158,Asn109, Asp108, Ala107, Trp106 |
T523 |
18041-18043 |
Sentence |
denotes |
8. |
T524 |
18045-18303 |
Sentence |
denotes |
Anaferine –6.43 19.24 µM Gly160, Asp108, Ala107, Trp93, Leu162, Glu161, Lys157 –6.0 39.69 µM Thr301, Tyr273, Tyr264, Trp106, Asp164, Pro248, Pro247, Met208, Arg166 –75.28 –68.35 –6.93 0 Ala68, Thr74, Phe79, Asp76, Pro77, Lys43, Arg65, Pro59, Leu58 |
T525 |
18304-18306 |
Sentence |
denotes |
9. |
T526 |
18308-18542 |
Sentence |
denotes |
Withasomnine –5.56 84.41 µM Asn109, Gln269, Cys270, Leu162, Gly160, Cys270 –7.2 4.50 µM Asp76, Pro59, Phe79, Leu80, Thr74, Ala68, Thr75, Arg65, Pro77, Leu58 –69.24 –69.24 0 0 Asp76, Pro77, Thr75, Leu80, Leu58, Pro59, Arg65 |
T527 |
18543-18546 |
Sentence |
denotes |
10. |
T528 |
18548-18796 |
Sentence |
denotes |
Procainamide –5.03 206.96 µM Glu161, Asn109, Leu162, Asp108, Gly160, Gln269, Cys270 –6.3 24.06 µM Asn109, Gln269, Leu162, Val159, His89, Asp108, Glu161, Gly160 –76.81 –66.66 –10.15 0 Leu162, Glu161, Gly160, Gln269,Asp108, Asn109,Cys270 |
T529 |
18797-18800 |
Sentence |
denotes |
11. |
T530 |
18802-19058 |
Sentence |
denotes |
Cinacalcet –6.44 19.17 µM Val159, Asp108, Gly160, Glu161, Leu162, His89, Val159 –8.8 344.50 nM Gly160, Asn109, Leu162, Gln269, Cys270, Glu161, Asp108 –81.40 –81.40 0 0 Thr158, Leu162, Glu161, Gly160, His89, Ser85, Ala86, Asn109, Val159, Asn108 |
T531 |
19059-19067 |
Sentence |
denotes |
Table 9. |
T532 |
19069-19154 |
Sentence |
denotes |
Binding energies of WS phytoconstituents with SARS–CoV main protease/3CL-pro (PBB ID: |
T533 |
19155-19248 |
Sentence |
denotes |
1P9U) in comparison to the FDA approved standard reference drugs (Oberadilol and Poziotinib). |
T534 |
19249-19300 |
Sentence |
denotes |
AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T535 |
19301-19303 |
Sentence |
denotes |
S. |
T536 |
19304-19307 |
Sentence |
denotes |
No. |
T537 |
19309-19459 |
Sentence |
denotes |
Ligands BE (kcal/mol) K d Interacting amino acids BE(kcal/mol) K d Interacting amino acids TE(kcal/mol) VDW HB EI Interacting amino acids |
T538 |
19460-19462 |
Sentence |
denotes |
1. |
T539 |
19464-19846 |
Sentence |
denotes |
Withaferin A –7.56 2.87 µM Thr47, Leu164, Pro188, Gln187, Glu165, Ser189, Met190, Gln191, Leu192, Asn168, Gly167, Leu166 –9.4 129.60 nM Gly126, Leu3, Cys284, Glu286, Arg4, Phe287, Lys5, Tyr280, Ser282, Ser279, Lys136 –116.60 –96.85 –19.75 0 Thr288, Thr290, Glu291, Arg294, Val299, Thr143, Tyr117, Cys116, Gly122, Ala115, Ser123, Gln8, Val150, Leu151, Glu152, Met6, Ser110 |
T540 |
19847-19849 |
Sentence |
denotes |
2. |
T541 |
19851-20173 |
Sentence |
denotes |
Withanolide A –8.93 285.01 nM Gly182, Gly183, Tyr184, Glu185, Leu192, Gln191, Met190, Ser189, Gln187, Val50 –10.9 345 nM Leu3, Arg4, Glu286, Tyr280, Phe287, Lys5, Cys284, Lys136, Ser279 –100.1 –84.54 –15.56 0 Phe272, Gly271, Leu268, Lys270, Asn269, Ser282, Leu283, Cys284, Asp285, Glu286, Lys136, Met198, Asn196 |
T542 |
20174-20176 |
Sentence |
denotes |
3. |
T543 |
20178-20513 |
Sentence |
denotes |
Withanolide B –8.12 1.12 µM Glu185, Gly183, Gly182, Tyr184, Ser189, Met190, Gln191, Leu192 –9.7 72.23 nM Lys270, Arg267, Leu268, Trp217, Phe218, Arg275, Gln256, Arg216, Thr254, Gly214 –104.12 –93.39 –10.74 0 Gly154, Asn153, Leu151, Glu152, Gly122, Tyr117, Ser123, Ala115, Thr143, Met6, Ser138, Ile140, Gln295, Arg294, Gly298 |
T544 |
20514-20516 |
Sentence |
denotes |
4. |
T545 |
20518-20867 |
Sentence |
denotes |
Withanolide D –7.68 2.34 µM Gly182, Tyr184, Glu185, Ser189, Met190, Gln191, Leu192, Glu193 –9.3 145.58 nM Glu54, Asn52, Tyr53, Arg40, Tyr81, Met57, Gln132, Ser131, Arg80, Val197, Thr239, Gly83 –111.44 –98.83 –12.61 0 Gly154, Asn153, Leu151, Glu152, Gln8, Gly122, Ser123,Cys116, Tyr117, Ala115, Thr143, Ile140, Ser138, Gln295, Met6, Arg294 |
T546 |
20868-20870 |
Sentence |
denotes |
5. |
T547 |
20872-21223 |
Sentence |
denotes |
Withanolide E –7.72 2.19 µM Glu185, Tyr184, Gly182, Gln132, Glu193, Gly194, Leu192, Gln191, Met190, Ser189 –9.0 240.98 nM Lys82, Gly83, Lys234, Ser131, Gln132, Ala107, Glu54, Tyr81, Arg80, Met57, Val197, Arg40, Thr239, Glu240 –104.61 –85.73 –18.88 0 Met6, Asn112, Ser110, Gln8, Val150, Glu152, Glu109, Thr288, Glu291, Gln295, Thr290, Arg294 |
T548 |
21224-21226 |
Sentence |
denotes |
6. |
T549 |
21228-21579 |
Sentence |
denotes |
Withanone –7.41 3.7 µM Glu193, Leu192, Gln191, Met190, Ser189, Glu185, Tyr184, Gly183, Gly182, Gln132 –9.1 212.78 nM Thr254, Arg216, Trp217, Arg275, Phe218, Lys260, Gln256, Leu268, Arg267, Lys270 –109.22 –100.63 –8.59 0 Arg294, Gln295, Ile140, Glu291, Glu152, Gly122, Ala115, Ser123, Met6, Gln8, Ala7, Ser110, Phe111, Val150, Asn112, Tyr149 |
T550 |
21580-21582 |
Sentence |
denotes |
7. |
T551 |
21584-21943 |
Sentence |
denotes |
Viscosalactone B –7.34 4.14 µM Leu192, Gly167, Leu166, Glu165, Leu164, Gln191, Met190, Ser189, Pro188, Gln187 –9.5 107.69 nM Lys5, Phe287, Glu286, Lys136, Met198, Asp285, Cys284, Leu283, Ser282, Arg4, Leu278, Ser279, Tyr280, Leu3 –100.67 –85.43 –15.24 0 Tyr125, Met6, Gly126, Lys5, Arg4, Leu3, Lys136, Leu278, Ser279, Tyr280, Cys284, Glu286, Phe287 |
T552 |
21944-21946 |
Sentence |
denotes |
8. |
T553 |
21948-22210 |
Sentence |
denotes |
Anaferine –6.19 29.14 µM Gly183, Glu185, Tyr184, Gly182, Gln191, Leu192, Glu193, Gln132 –6.8 10.34 µM Arg294, Gln295, Glu291, Gln8, Ser110, Lys5, Gly126, Ala7, Met6, Ser123, Gly122 –74.07 –60.38 –13.68 0 Tyr280, Leu3, Arg4, Lys5,Gly126, Tyr125, Val124 |
T554 |
22211-22213 |
Sentence |
denotes |
9. |
T555 |
22215-22526 |
Sentence |
denotes |
Withasomnine –6.06 36.09 µM Tyr53, Ile51, Ser189, Gln191, Gln187, Pro188, Asp186, Thr47, His41, Leu164, Glu165 –7.1 6.20 µM Arg294, Met6, Gln295, Glu291, Lys5, Asn112, Phe111, Gln8, Val150, Ser110, Leu151 –71.58 –63.14 –8.44 0 Ala79, Val60, Gly194, Met57, Ser58, Glu193, Gln132, Val197, Arg80, Thr195 |
T556 |
22527-22530 |
Sentence |
denotes |
10. |
T557 |
22532-22861 |
Sentence |
denotes |
Oberadilol –4.54 469.45 µM Glu185, Tyr184, Gly183, Gly182, Gln132, Glu193, Leu192, Gln191, Met190, Ser189 –8.7 401.24 nM Glu54, Tyr53, Arg40, Gly83, Val197, Arg80, Ser131, Thr239, Ala107, Glu240, Lys234, Lys82, Tyr81 –95.18 –81.58 –13.60 0 Trp217, Arg267, Leu268, Lys270, Phe272, Gly271, Gly273, Gly274, Arg275, Val219 |
T558 |
22862-22865 |
Sentence |
denotes |
11. |
T559 |
22867-23216 |
Sentence |
denotes |
Poziotinib –6.41 20.18 µM Thr195, Gly194, Glu193, Leu192, Gln191, Met159, Tyr184, Gly182, Gln132 –8.4 710.54 nM Met190, Gly167, Leu166, Ser189, Glu165, Ala141, Ile140, Phe139, Cys144, Thr47, His41, Pro188, Leu164, Gln187, Gln191 –103.87 –94.39 –9.49 0 Arg275, Gly274, Gly273, Trp217, Thr220, Asn221, Gly271, Lys270, Thr222, Arg267, Leu263 |
T560 |
23217-23226 |
Sentence |
denotes |
Table 10. |
T561 |
23228-23315 |
Sentence |
denotes |
Binding energies of WS phytoconstituents with SARS-CoV-2 main protease/3CL-pro (PDB ID: |
T562 |
23316-23409 |
Sentence |
denotes |
6LU7) in comparison to the FDA approved standard reference drugs (Oberadilol and Poziotinib). |
T563 |
23410-23461 |
Sentence |
denotes |
AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T564 |
23462-23464 |
Sentence |
denotes |
S. |
T565 |
23465-23468 |
Sentence |
denotes |
No. |
T566 |
23470-23621 |
Sentence |
denotes |
Ligands BE (kcal/mol) K d Interacting amino acids BE(kcal/mol) Kd Interacting amino acids TE(kcal/mol) VDW HB EI Interacting amino acids |
T567 |
23622-23624 |
Sentence |
denotes |
1. |
T568 |
23626-23942 |
Sentence |
denotes |
Withaferin A –2.85 8.21 mM Tyr126, Gln127, Gly138, Va171, Gly170, Lys137, Lys5 –8.4 670.89 nM Arg105, Ile106, Val104, Ser158, Phe294,Phe112, Phe8, Thr111, Asp295, Asn151,Gln110, Thr292, Gln107 –98.51 –78.64 –19.87 0 Gly143, Ser144, Cys145, His163, Met165, Glu166, Gln189, Thr190, Asn142, Leu141, Phe140 |
T569 |
23943-23945 |
Sentence |
denotes |
2. |
T570 |
23947-24256 |
Sentence |
denotes |
Withanolide A –5.26 139.0 µM Lys5, Gln127, Tyr126, Val125, Ser139, Lys137, Glu288, Glu290 –8.5 592.38 nM Asp289, Thr199, Glu290, Arg131, Lys137, Tyr239, Leu272, Leu287, Leu286, Met276, Gly275 –91.61 –70.18 –21.43 0 Gly179, Asn180, Phe181, Asn84, Cys85, Arg40, Phe185, Tyr54, Asn53, Pro52, Arg188 |
T571 |
24257-24259 |
Sentence |
denotes |
3. |
T572 |
24261-24606 |
Sentence |
denotes |
Withanolide B –5.67 69.79 µM Ser139, Gly138, Lys137, Cys128, Glu290, Gln127, Tyr126, Val125 –8.3 845.65 nM Leu287, Tyr239, Tyr237, Leu272, Leu286, Asn238, Thr199, Asp289, Glu288, Arg131, Glu290, Lys137 –89.17 –72.53 –16.64 0 His163, His164, Met165, Cys145, Ser144, Phe140, Leu141, Asp142, Gly143, Thr25, Met149, Thr45, Ser46, Thr24 |
T573 |
24607-24609 |
Sentence |
denotes |
4. |
T574 |
24611-24954 |
Sentence |
denotes |
Withanolide D –5.55 85.19 µM Tyr126, Gln127, Gly138, Ser139, His172, Gly170, Lys137, Lys5 –8.7 424.04 nM Tyr239, Leu287, Val204, Leu272, Tyr237, Asn238, Arg131, Lys137, Thr199, Leu286, Asp289 –104.35 –85.29 –19.06 0 Thr26, Leu27, Cys145, Gly143, Ser144, His164, Asn142, Met165, Glu166, Pro168, Thr190, Gln189, Arg188, Met49,His41 |
T575 |
24955-24957 |
Sentence |
denotes |
5. |
T576 |
24959-25247 |
Sentence |
denotes |
Withanolide E –5.2 154.68 µM Tyr126, Gln127, Lys5, Glu290, Lys137, Gly138, Ser139 –8.1 1.16 µM Asn238, Asp289, Arg131, Lys137, Thr199, Leu286, Leu287, Tyr239, Leu272, Tyr237 –97.42 –70.98 –26.44 0 Arg131,Asn133, Ala194, Gly195, Asp289, Asp197, Thr196, Thr199, Thr198, Asn238 |
T577 |
25248-25250 |
Sentence |
denotes |
6. |
T578 |
25252-25632 |
Sentence |
denotes |
Withanone –6.14 31.77 µM Val125, Tyr126, Gln127, Cys128, Ser139, Gly138, Lys137, Ala129, Glu290 –8.4 707.34 nM Leu286, Tyr239, Lys137, Asp197, Arg131, Thr198, Thr199, Asn238, Tyr237, Met276, Gly275, Leu272, Leu271, Leu287 –100.18 –88.69 –11.49 0 Thr24, Thr25, Thr26, His41, Gly143, Cys145, Ser144, His164, His163, His172, Phe140, Glu166, Leu141, Asn142, Met49, Ser46 |
T579 |
25633-25635 |
Sentence |
denotes |
7. |
T580 |
25637-26009 |
Sentence |
denotes |
Viscosalactone B –4.86 274.4 µM Val104, Asn151, Phe8, Arg298, Gln127, Asp295, Phe294, Thr111, Thr292, Gln110, Gln107, Ile106, Arg105 –8.2 969.04 nM Gly278, Lys137, Asp289, Arg131, Tyr239, Thr199, Leu287, Leu286, Leu272, Gly275,Met276, Asn274, Asn277 –97.17 –67.45 –29.72 0 Tyr239, Asn238, Tyr237, Thr199, Leu287, Leu286, Ala285, Gly278, Asn277, Met276,Gly275 |
T581 |
26010-26012 |
Sentence |
denotes |
8. |
T582 |
26014-26330 |
Sentence |
denotes |
Anaferine –5.13 174.99 µM Glu290, Cys128, Lys5, Gln127, Tyr126, Lys137 –5.7 66.02 µM Cys145, Asn142, Leu141, Phe140,Glu166, Ser144,His172,Met165, His164, Gln189, Asp187, Arg188, Met49, His41 –76.27 –67.75 –8.52 0 Thr25, Thr26, Leu27, Cys145, His163, Met165, Glu166,His172, Phe140, Leu141,Ser144, Gly143 |
T583 |
26331-26333 |
Sentence |
denotes |
9. |
T584 |
26335-26631 |
Sentence |
denotes |
Withasomnine –5.22 149.2 µM Ser158, Ile152, Asp153, Asn151, Thr111, Asp295, Phe294, Thr292, Gln110 –6.2 28.68 µM Ile152, Phe8, Val104, Ile106, Gln110, Thr111, Asn151, Asp153, Phe294 –71.96 –60.03 –11.94 0 His41, His163, His164, Met165, Cys145, Ser144, His172, Glu166, Phe140, Leu141 |
T585 |
26632-26635 |
Sentence |
denotes |
10. |
T586 |
26637-26961 |
Sentence |
denotes |
Oberadilol –2.23 23.18 mM Lys137, Glu290, Gln127, Tyr126, Lys5 –6.9 9.00 µM Leu286, Tyr239, Lys137, Asp197, Arg131, Thr198, Thr199, Asn238, Tyr237, Met276, Gly275, Leu272, Leu271, Leu287 –100.96 –94.41 –6.55 0 His163, Cys145, His164, Met165, Asn142, Glu166, Leu141, Leu167, Pro168, Gln189, Met49, Asp187, His41 |
T587 |
26962-26965 |
Sentence |
denotes |
11. |
T588 |
26967-27341 |
Sentence |
denotes |
Poziotinib –4.49 513.87 µM Tyr126, Gln127, Cys128, Lys5, Ala129, Glu290, Lys137, Gly138, Ser139 7.7 2.20 µM Gly278, Ala285, Gly275, Tyr237, Leu272, Asn238, Tyr239, Thr199, Asp289, Arg131, Leu286, Lys137, Leu287, Met276 –111.32 –96.66 –14.66 0 His41, Cys145, His164, Asp187, Arg188, Met165, Gln189, Glu166, Thr190, Ala191, Gln192, Pro168, Phe140, Leu141, Asn142 |
T589 |
27342-27351 |
Sentence |
denotes |
Table 11. |
T590 |
27353-27445 |
Sentence |
denotes |
Binding energies of WS phytoconstituents with Nsp-10/Nsp-16 complex from SARS-CoV-2 (PDB ID: |
T591 |
27446-27545 |
Sentence |
denotes |
6W75) in comparison to the FDA approved standard reference drugs (Losartan and Hydroxychloroquine). |
T592 |
27546-27597 |
Sentence |
denotes |
AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T593 |
27598-27600 |
Sentence |
denotes |
S. |
T594 |
27601-27604 |
Sentence |
denotes |
No. |
T595 |
27606-27759 |
Sentence |
denotes |
Ligands BE (kcal/mol) K d Interacting amino acids BE(kcal/mol) K d Interacting amino acids TE(kcal/mol) VDW HB EI Interacting amino acids |
T596 |
27760-27762 |
Sentence |
denotes |
1. |
T597 |
27764-28207 |
Sentence |
denotes |
Withaferin A –9.33 144.58 nM Asp6906, Asn7095, Ser6907, Thr6908, Leu7093, Leu6909, Val7092, Ser7089, Ser7090, Val7092 –10.0 40.98 nM Lys6968, Glu7001, Ser6999, Thr6970, Ser7000, Asn6996, Lys6844, Asn6841, Tyr6930, Gly6871, Asp6928, Pro6932, Ser6872, Met6929, Gly6869, Leu6898, Asp6897, Asn6899 –99.04 –82.04 –17 0 Tyr6828, Ser6999, Ser7000, Thr6970, Glu7001, Asn6996, Lys6844, Lys6968, Asn6841, Asp6928, Tyr6930, Gly6871, Ser6872 |
T598 |
28208-28210 |
Sentence |
denotes |
2. |
T599 |
28212-28651 |
Sentence |
denotes |
Withanolide A –10.38 24.67 nM Ala6905, Asp6906, Lys4346, Ser6907, Thr6908, Leu6909, Ile6910, Ser7090, Leu7093, Val7092, Ser7090 –10.4 23.67 nM Pro6932, Tyr6930, Asn6899, Asp6931, Leu6898, Asp6897, Met6929, Gly6869, Ser6872, Gly6871, Asn6841, Lys6844, Lys6968, Glu7001, Thr6970, Ser6999 –101.39 –78.76 –22.63 0 Gly6871, Gly6869, Asn6899, Asp6897, Leu6898, Asp6912, Cys6913, Phe6947, Asp6931, Lys6933, Pro6932, Met6929, Asp6928 |
T600 |
28652-28654 |
Sentence |
denotes |
3. |
T601 |
28656-29101 |
Sentence |
denotes |
Withanolide B –10.09 39.9 nM Lys4346, Cys4330, His4333, Val6902, Ser6903, Phe6901, Asp6900, Thr6908, Ile6910, Leu6909, Val7092, Ser7090 –11.0 1.98 nM Lys6844, Asn6841, Asp6928, Lys6968, Tyr6930, Gly6871, Gly6869, Asp6931, Leu6898, Cys6913, Met6929, Phe6947, Asp6897, Asn6899, Ser6872, Pro6932 –103.08 –95.57 –7.51 0 Val4274, Ile4334, Asp4335, Ile4334, Cys4332, Arg4331, Thr4292, Ile4291, Pro4290, Gln4289, Ala4271, Phe4272, Ala4273 |
T602 |
29102-29104 |
Sentence |
denotes |
4. |
T603 |
29106-29526 |
Sentence |
denotes |
Withanolide D –9.58 94.36 nM Val7092, Ser7089, Ser7090, Asp7091, Leu6909, Thr6908, Ser6907, Asp6906, Lys4346 –10.5 27.89 nM Lys6844, Asn6841, Asp6928, Ser6872, Tyr6930, Gly6871, Met6929, Gly6869, Leu6898, Asp6897, Asp6899, Pro6932, Asp6931, Lys6968, Thr6970, Glu7001, Ser6999 –110.77 –85.34 –25.43 0 Gly4341, Phe4342, Cys4343, Asp6906, Lys4346, Gly4347, Lys4348, Val4310, Arg6884, Thr6889, Gly6890, Asn7096 |
T604 |
29527-29529 |
Sentence |
denotes |
5. |
T605 |
29531-29915 |
Sentence |
denotes |
Withanolide E –8.96 272.55 nM His4333, Phe6901, Val6902, Leu6909, Ser6903, Thr6908, Lys4346, Ser6907, Asp6906, Val7092 –9.8 62.56 nM His4333, Cys4332, Phe4272, Thr4292, Ile4291, Ala4271, Gln4289, Asn4293, Arg4331, Val6876, Lys6874, Gly6875, Val6902 –104.92 –92.21 –12.72 0 Tyr7020, Leu6820, Glu6821, Lys6822, Asp6942, Trp6974, Asn6941, Glu6940, Glu6971, His6972, Lys6939 |
T606 |
29916-29918 |
Sentence |
denotes |
6. |
T607 |
29920-30280 |
Sentence |
denotes |
Withanone –10.17 34.9 nM Cys4330, His4333, Val6901, Asp6900, Phe6901, Thr6908, Ile6910, Leu6909, Ser7090, Val7092 –9.8 63.56 nM Val7092, Asp7091, Thr6915, Leu7093, Asp6912, Gly6911, Leu6898, Ser7089, Ile6910, Leu6909,Ser7090 –105.42 –91.03 –14.39 0 Ala4273, Cys4332, Val4274, Ile4334, Ala4276, Asp4335, Pro4337, Tyr4329, His4336, Asn4338, Pro4339 |
T608 |
30281-30283 |
Sentence |
denotes |
7. |
T609 |
30285-30717 |
Sentence |
denotes |
Viscosalactone B –9.03 238.8 nM Asp6900, Leu7093, Val7092, Gly6911, Asp7091, Ser7090, Ile6910, Leu6909, Thr6908, Ser6907, Asp6906 –9.9 57.78 nM His4336, Ile4334, Asp4335, Tyr4329, Cys4330, His4333, Val6902, Ile6910, Asp6900, Val7092, Leu6909, Ser7089, Ser7090, Thr6908 –119.11 –103.53 –15.58 0 Thr4292, Ile4291, Pro4290, Gln4289, Tyr4283, Ala4271, Phe4272, Arg4331, Cys4332, Ile4334, Asp4335, Tyr4329, Val4274, Ala4273 |
T610 |
30718-30720 |
Sentence |
denotes |
8. |
T611 |
30722-31005 |
Sentence |
denotes |
Anaferine –7.1 6.25 µM Asp4335, Asp6900, Phe6901, Ile6910, Thr6908 –6.3 22.67 nM Leu6819, Tyr7020, Val7021, Asp7018, Leu6820, Met6818, Arg6817 –86.35 –74.35 –12 0 Gly6911, Asp6912, Cys6913, Phe6947, Leu6898, Asp6897, Gly6871, Gly6869, Met6929, Tyr6930, Asp6928, Phe6947 |
T612 |
31006-31008 |
Sentence |
denotes |
9. |
T613 |
31010-31281 |
Sentence |
denotes |
Withasomnine –6.06 36.03 µM Val7092, Asp7091, Ser7090, Ile6910, Leu6909, Ser7089 –8.0 1.23 µM Tyr7020, Leu6820, Met6818, Leu6819, Ala7024, Arg6817, Val7021, Asp7018 –74.52 –65.96 –8.56 0 Thr4292,Arg4331, Ile4291, Pro4290, Gln4289, Tyr4283, Phe4272, Ala4271, |
T614 |
31282-31285 |
Sentence |
denotes |
10. |
T615 |
31287-31666 |
Sentence |
denotes |
Losartan –6.49 17.54 µM Thr6908, Leu6909, Ile6910, Asp6900, Ser7090, Ser7089, Val7092 –8.3 780.68 nM Ala4273, Val4274, Asp4335, His4333, Ala4271, Ile4334, Pro4290, Gln4289, Thr4292, Ile4291, Cys4332, Phe4272, Arg4331, Gly6875, Lys6874, Val6876 –104.17 –75.33 –28.84 0 Gln6957, Gln6956, Glu7062, Lys6958, Lys6921, Ile7080, Leu6959, Leu6961, Tyr7009, Ile6955, His6984 |
T616 |
31667-31670 |
Sentence |
denotes |
11. |
T617 |
31672-32116 |
Sentence |
denotes |
Hydroxychloroquine –4.93 244.14 µM Thr6908, Ile6910, Ser6907, Leu6909, Ser7090, Ser7089, Val7092 –6.7 11.70 µM Gly6869, Gly6871, Asn6841, Tyr6930, Pro6932, Ser6872, Asp6873, Asn6899, Asp6897,Leu6898, Met6929 –80.22 –69.44 −10.78 0 Lys6968, Asp6928, Gly6871, Gly6869, Met6929, Asp6897,A sn6899, Leu6898, Tyr6930, Pro6932, Ser6872 Withasomnine was found to bind near or at the active site of SARS-Co-V main protease 3CL-pro (PDB ID: |
T618 |
32117-32362 |
Sentence |
denotes |
1P9U; Table 9), whereas anaferine was found to interact with the active site residues Cys145, Glu166, Ser144, Met165, His163, His164, Gln189, Asp187, Arg188, Met49 and His41 present at the active site of SARS-CoV-2 main protease 3CL-pro (PDB ID: |
T619 |
32363-32379 |
Sentence |
denotes |
6LU7; Table 10). |
T620 |
32380-32566 |
Sentence |
denotes |
The 3CL-pro active site has been found to be evolutionarily conserved between SARS-CoV and SARS-CoV-2 (Báez-Santos et al., 2015; Chen et al., 2020; Guy et al., 2005; Zhang et al., 2020). |
T621 |
32567-32759 |
Sentence |
denotes |
In the same manner, the other seven phytoconstituents also displayed potent binding to the active site of SARS-CoV-2 3CL-pro except viscosalactone B as predicted by AutoDock vina and iGEMDOCK. |
T622 |
32760-32830 |
Sentence |
denotes |
The active site residues have been written in bold in Tables 9 and 10. |
T623 |
32831-32951 |
Sentence |
denotes |
As far as viral PL-pro and human ACE2 are concerned, WS phytoconstituents displayed allosteric binding to these enzymes. |
T624 |
32952-33074 |
Sentence |
denotes |
On the other hand, withanolide A displayed strong binding to SARS-CoV spike glycoprotein (Table 6; BE: −9.78 kcal/mol, Kd: |
T625 |
33075-33149 |
Sentence |
denotes |
67.23 nM), SARS-CoV-2 spike glycoprotein (Table 7; BE: −7.18 kcal/mol, Kd: |
T626 |
33150-33224 |
Sentence |
denotes |
5.48 µM), SARS-CoV 3CL-pro main protease (Table 9; BE: –8.93 kcal/mol, Kd: |
T627 |
33225-33307 |
Sentence |
denotes |
285.01 nM) and SARS-CoV-2 Nsp10/Nsp-16 complex (Table 11; BE: −10.38 kcal/mol, Kd: |
T628 |
33308-33318 |
Sentence |
denotes |
24.67 nM). |
T629 |
33319-33501 |
Sentence |
denotes |
Interestingly, withanolide A exhibited almost 1000× times stronger binding to SARS-CoV main protease as compared to standard reference drugs arbidol (Table 6; BE: −4.91 kcal/mol, Kd: |
T630 |
33502-33569 |
Sentence |
denotes |
251.65 µM) and hydroxychloroquine (Table 6; BE: −5.25 kcal/mol, Kd: |
T631 |
33570-33581 |
Sentence |
denotes |
142.18 µM). |
T632 |
33582-33765 |
Sentence |
denotes |
The same binding profile was observed for withanolide A with respect to SARS-CoV-2 spike glycoprotein as compared to standard reference drugs arbidol (Table 7; BE: −3.14 kcal/mol, Kd: |
T633 |
33766-33831 |
Sentence |
denotes |
4.99 mM) and hydroxychloroquine (Table 7; BE: −2.48 kcal/mol, Kd: |
T634 |
33832-33842 |
Sentence |
denotes |
15.11 mM). |
T635 |
33843-33998 |
Sentence |
denotes |
Withanolide A also displayed a 1000× stronger binding to Nsp-10/Nsp-16 complex from SARS-CoV-2 in comparison to losartan (Table 11; BE: −6.49 kcal/mol, Kd: |
T636 |
33999-34066 |
Sentence |
denotes |
17.54 µM) and hydroxychloroquine (Table 11; BE: −4.93 kcal/mol, Kd: |
T637 |
34067-34077 |
Sentence |
denotes |
244.14 µM) |
T638 |
34078-34185 |
Sentence |
denotes |
Withanone also displayed significant binding to SARS-Cov-2 main protease (Table 10; BE: −6.14 kcal/mol, Kd: |
T639 |
34186-34282 |
Sentence |
denotes |
31.77 µM) in comparison to standard reference drug oberadilol (Table 10; BE: −2.23 kcal/mol, Kd: |
T640 |
34283-34293 |
Sentence |
denotes |
23.18 mM). |
T641 |
34294-34461 |
Sentence |
denotes |
The best docking poses of the WS phytoconstituents with respect to the human ACE2 receptor and viral target proteins have been depicted in Table 12 (Tables 12.1–12.7). |
T642 |
34462-34566 |
Sentence |
denotes |
Binding studies on WS constituents to unbound spike receptor-binding domain (RBD) of SARS-CoV-2 (PDB ID: |
T643 |
34567-34760 |
Sentence |
denotes |
6M0J) and binding of WS phytoconstituents with SARS-CoV-2 spike receptor-binding domain (RBD) bound with ACE2 have been provided as supplementary data files ST1, SFI, ST2 and SF2, respectively. |
T644 |
34761-34770 |
Sentence |
denotes |
Table 12. |
T645 |
34772-34861 |
Sentence |
denotes |
Best docking poses of human and viral target proteins with selected WS phytoconstituents. |
T646 |
34862-34916 |
Sentence |
denotes |
Ligands AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T647 |
34917-34922 |
Sentence |
denotes |
12.1. |
T648 |
34923-34999 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with human ACE2 receptor (PDB ID: |
T649 |
35000-35087 |
Sentence |
denotes |
1O8A) in comparison to the FDA approved standard reference drugs (Arbidol and Losartan) |
T650 |
35088-35100 |
Sentence |
denotes |
Withaferin A |
T651 |
35101-35114 |
Sentence |
denotes |
Withanolide A |
T652 |
35115-35128 |
Sentence |
denotes |
Withanolide B |
T653 |
35129-35142 |
Sentence |
denotes |
Withanolide D |
T654 |
35143-35156 |
Sentence |
denotes |
Withanolide E |
T655 |
35157-35166 |
Sentence |
denotes |
Withanone |
T656 |
35167-35183 |
Sentence |
denotes |
Viscosalactone B |
T657 |
35184-35193 |
Sentence |
denotes |
Anaferine |
T658 |
35194-35206 |
Sentence |
denotes |
Withasomnine |
T659 |
35207-35214 |
Sentence |
denotes |
Arbidol |
T660 |
35215-35223 |
Sentence |
denotes |
Losartan |
T661 |
35224-35229 |
Sentence |
denotes |
12.2. |
T662 |
35230-35314 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with SARS-CoV spike glycoprotein (PDB ID: |
T663 |
35315-35412 |
Sentence |
denotes |
5WRG) in comparison to the FDA approved standard reference drugs (Arbidol and Hydroxychloroquine) |
T664 |
35413-35425 |
Sentence |
denotes |
Withaferin A |
T665 |
35426-35439 |
Sentence |
denotes |
Withanolide A |
T666 |
35440-35453 |
Sentence |
denotes |
Withanolide B |
T667 |
35454-35467 |
Sentence |
denotes |
Withanolide D |
T668 |
35468-35481 |
Sentence |
denotes |
Withanolide E |
T669 |
35482-35491 |
Sentence |
denotes |
Withanone |
T670 |
35492-35508 |
Sentence |
denotes |
Viscosalactone B |
T671 |
35509-35518 |
Sentence |
denotes |
Anaferine |
T672 |
35519-35531 |
Sentence |
denotes |
Withasomnine |
T673 |
35532-35539 |
Sentence |
denotes |
Arbidol |
T674 |
35540-35558 |
Sentence |
denotes |
Hydroxychloroquine |
T675 |
35559-35564 |
Sentence |
denotes |
12.3. |
T676 |
35565-35651 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with SARS-CoV-2 spike glycoprotein (PDB ID: |
T677 |
35652-35745 |
Sentence |
denotes |
6VXX) in comparison to FDA approved standard reference drugs (Arbidol and Hydroxychloroquine) |
T678 |
35746-35758 |
Sentence |
denotes |
Withaferin A |
T679 |
35759-35772 |
Sentence |
denotes |
Withanolide A |
T680 |
35773-35786 |
Sentence |
denotes |
Withanolide B |
T681 |
35787-35800 |
Sentence |
denotes |
Withanolide D |
T682 |
35801-35814 |
Sentence |
denotes |
Withanolide E |
T683 |
35815-35824 |
Sentence |
denotes |
Withanone |
T684 |
35825-35841 |
Sentence |
denotes |
Viscosalactone B |
T685 |
35842-35851 |
Sentence |
denotes |
Anaferine |
T686 |
35852-35864 |
Sentence |
denotes |
Withasomnine |
T687 |
35865-35872 |
Sentence |
denotes |
Arbidol |
T688 |
35873-35891 |
Sentence |
denotes |
Hydroxychloroquine |
T689 |
35892-35897 |
Sentence |
denotes |
12.4. |
T690 |
35898-35989 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with papain like protease of SARS-CoV-2 (PDB ID: |
T691 |
35990-36084 |
Sentence |
denotes |
6W9C) in comparison to the FDA approved standard reference drugs (Procainamide and Cinacalcet) |
T692 |
36085-36097 |
Sentence |
denotes |
Withaferin A |
T693 |
36098-36111 |
Sentence |
denotes |
Withanolide A |
T694 |
36112-36125 |
Sentence |
denotes |
Withanolide B |
T695 |
36126-36139 |
Sentence |
denotes |
Withanolide D |
T696 |
36140-36153 |
Sentence |
denotes |
Withanolide E |
T697 |
36154-36163 |
Sentence |
denotes |
Withanone |
T698 |
36164-36180 |
Sentence |
denotes |
Viscosalactone B |
T699 |
36181-36190 |
Sentence |
denotes |
Anaferine |
T700 |
36191-36203 |
Sentence |
denotes |
Withasomnine |
T701 |
36204-36216 |
Sentence |
denotes |
Procainamide |
T702 |
36217-36227 |
Sentence |
denotes |
Cinacalcet |
T703 |
36228-36233 |
Sentence |
denotes |
12.5. |
T704 |
36234-36321 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with SARS-CoV main protease/3CL-pro (PBB ID: |
T705 |
36322-36414 |
Sentence |
denotes |
1P9U) in comparison to the FDA approved standard reference drugs (Oberadilol and Poziotinib) |
T706 |
36415-36427 |
Sentence |
denotes |
Withaferin A |
T707 |
36428-36441 |
Sentence |
denotes |
Withanolide A |
T708 |
36442-36455 |
Sentence |
denotes |
Withanolide B |
T709 |
36456-36469 |
Sentence |
denotes |
Withanolide D |
T710 |
36470-36483 |
Sentence |
denotes |
Withanolide E |
T711 |
36484-36493 |
Sentence |
denotes |
Withanone |
T712 |
36494-36510 |
Sentence |
denotes |
Viscosalactone B |
T713 |
36511-36520 |
Sentence |
denotes |
Anaferine |
T714 |
36521-36533 |
Sentence |
denotes |
Withasomnine |
T715 |
36534-36544 |
Sentence |
denotes |
Oberadilol |
T716 |
36545-36555 |
Sentence |
denotes |
Poziotinib |
T717 |
36556-36561 |
Sentence |
denotes |
12.6. |
T718 |
36562-36651 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with SARS-CoV-2 main protease/3CL-pro (PDB ID: |
T719 |
36652-36744 |
Sentence |
denotes |
6LU7) in comparison to the FDA approved standard reference drugs (Oberadilol and Poziotinib) |
T720 |
36745-36757 |
Sentence |
denotes |
Withaferin A |
T721 |
36758-36771 |
Sentence |
denotes |
Withanolide A |
T722 |
36772-36785 |
Sentence |
denotes |
Withanolide B |
T723 |
36786-36799 |
Sentence |
denotes |
Withanolide D |
T724 |
36800-36813 |
Sentence |
denotes |
Withanolide E |
T725 |
36814-36823 |
Sentence |
denotes |
Withanone |
T726 |
36824-36840 |
Sentence |
denotes |
Viscosalactone B |
T727 |
36841-36850 |
Sentence |
denotes |
Anaferine |
T728 |
36851-36863 |
Sentence |
denotes |
Withasomnine |
T729 |
36864-36874 |
Sentence |
denotes |
Oberadilol |
T730 |
36875-36885 |
Sentence |
denotes |
Poziotinib |
T731 |
36886-36891 |
Sentence |
denotes |
12.7. |
T732 |
36892-36986 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with Nsp-10/Nsp-16 complex from SARS-CoV-2 (PDB ID: |
T733 |
36987-37085 |
Sentence |
denotes |
6W75) in comparison to the FDA approved standard reference drugs (Losartan and Hydroxychloroquine) |
T734 |
37086-37098 |
Sentence |
denotes |
Withaferin A |
T735 |
37099-37112 |
Sentence |
denotes |
Withanolide A |
T736 |
37113-37126 |
Sentence |
denotes |
Withanolide B |
T737 |
37127-37140 |
Sentence |
denotes |
Withanolide D |
T738 |
37141-37154 |
Sentence |
denotes |
Withanolide E |
T739 |
37155-37164 |
Sentence |
denotes |
Withanone |
T740 |
37165-37181 |
Sentence |
denotes |
Viscosalactone B |
T741 |
37182-37191 |
Sentence |
denotes |
Anaferine |
T742 |
37192-37204 |
Sentence |
denotes |
Withasomnine |
T743 |
37205-37213 |
Sentence |
denotes |
Losartan |
T744 |
37214-37232 |
Sentence |
denotes |
Hydroxychloroquine |