Id |
Subject |
Object |
Predicate |
Lexical cue |
T625 |
4-78 |
Sentence |
denotes |
67.23 nM), SARS-CoV-2 spike glycoprotein (Table 7; BE: −7.18 kcal/mol, Kd: |
T626 |
79-153 |
Sentence |
denotes |
5.48 µM), SARS-CoV 3CL-pro main protease (Table 9; BE: –8.93 kcal/mol, Kd: |
T627 |
154-236 |
Sentence |
denotes |
285.01 nM) and SARS-CoV-2 Nsp10/Nsp-16 complex (Table 11; BE: −10.38 kcal/mol, Kd: |
T628 |
237-247 |
Sentence |
denotes |
24.67 nM). |
T629 |
248-430 |
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 |
431-498 |
Sentence |
denotes |
251.65 µM) and hydroxychloroquine (Table 6; BE: −5.25 kcal/mol, Kd: |
T631 |
499-510 |
Sentence |
denotes |
142.18 µM). |
T632 |
511-694 |
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 |
695-760 |
Sentence |
denotes |
4.99 mM) and hydroxychloroquine (Table 7; BE: −2.48 kcal/mol, Kd: |
T634 |
761-771 |
Sentence |
denotes |
15.11 mM). |
T635 |
772-927 |
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 |
928-995 |
Sentence |
denotes |
17.54 µM) and hydroxychloroquine (Table 11; BE: −4.93 kcal/mol, Kd: |
T637 |
996-1006 |
Sentence |
denotes |
244.14 µM) |
T638 |
1007-1114 |
Sentence |
denotes |
Withanone also displayed significant binding to SARS-Cov-2 main protease (Table 10; BE: −6.14 kcal/mol, Kd: |
T639 |
1115-1211 |
Sentence |
denotes |
31.77 µM) in comparison to standard reference drug oberadilol (Table 10; BE: −2.23 kcal/mol, Kd: |
T640 |
1212-1222 |
Sentence |
denotes |
23.18 mM). |
T641 |
1223-1390 |
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 |
1391-1495 |
Sentence |
denotes |
Binding studies on WS constituents to unbound spike receptor-binding domain (RBD) of SARS-CoV-2 (PDB ID: |
T643 |
1496-1689 |
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 |
1690-1699 |
Sentence |
denotes |
Table 12. |
T645 |
1701-1790 |
Sentence |
denotes |
Best docking poses of human and viral target proteins with selected WS phytoconstituents. |
T646 |
1791-1845 |
Sentence |
denotes |
Ligands AutoDock v4.2.6 AutoDock vina iGEMDOCK v2.1 |
T647 |
1846-1851 |
Sentence |
denotes |
12.1. |
T648 |
1852-1928 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with human ACE2 receptor (PDB ID: |
T649 |
1929-2016 |
Sentence |
denotes |
1O8A) in comparison to the FDA approved standard reference drugs (Arbidol and Losartan) |
T650 |
2017-2029 |
Sentence |
denotes |
Withaferin A |
T651 |
2030-2043 |
Sentence |
denotes |
Withanolide A |
T652 |
2044-2057 |
Sentence |
denotes |
Withanolide B |
T653 |
2058-2071 |
Sentence |
denotes |
Withanolide D |
T654 |
2072-2085 |
Sentence |
denotes |
Withanolide E |
T655 |
2086-2095 |
Sentence |
denotes |
Withanone |
T656 |
2096-2112 |
Sentence |
denotes |
Viscosalactone B |
T657 |
2113-2122 |
Sentence |
denotes |
Anaferine |
T658 |
2123-2135 |
Sentence |
denotes |
Withasomnine |
T659 |
2136-2143 |
Sentence |
denotes |
Arbidol |
T660 |
2144-2152 |
Sentence |
denotes |
Losartan |
T661 |
2153-2158 |
Sentence |
denotes |
12.2. |
T662 |
2159-2243 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with SARS-CoV spike glycoprotein (PDB ID: |
T663 |
2244-2341 |
Sentence |
denotes |
5WRG) in comparison to the FDA approved standard reference drugs (Arbidol and Hydroxychloroquine) |
T664 |
2342-2354 |
Sentence |
denotes |
Withaferin A |
T665 |
2355-2368 |
Sentence |
denotes |
Withanolide A |
T666 |
2369-2382 |
Sentence |
denotes |
Withanolide B |
T667 |
2383-2396 |
Sentence |
denotes |
Withanolide D |
T668 |
2397-2410 |
Sentence |
denotes |
Withanolide E |
T669 |
2411-2420 |
Sentence |
denotes |
Withanone |
T670 |
2421-2437 |
Sentence |
denotes |
Viscosalactone B |
T671 |
2438-2447 |
Sentence |
denotes |
Anaferine |
T672 |
2448-2460 |
Sentence |
denotes |
Withasomnine |
T673 |
2461-2468 |
Sentence |
denotes |
Arbidol |
T674 |
2469-2487 |
Sentence |
denotes |
Hydroxychloroquine |
T675 |
2488-2493 |
Sentence |
denotes |
12.3. |
T676 |
2494-2580 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with SARS-CoV-2 spike glycoprotein (PDB ID: |
T677 |
2581-2674 |
Sentence |
denotes |
6VXX) in comparison to FDA approved standard reference drugs (Arbidol and Hydroxychloroquine) |
T678 |
2675-2687 |
Sentence |
denotes |
Withaferin A |
T679 |
2688-2701 |
Sentence |
denotes |
Withanolide A |
T680 |
2702-2715 |
Sentence |
denotes |
Withanolide B |
T681 |
2716-2729 |
Sentence |
denotes |
Withanolide D |
T682 |
2730-2743 |
Sentence |
denotes |
Withanolide E |
T683 |
2744-2753 |
Sentence |
denotes |
Withanone |
T684 |
2754-2770 |
Sentence |
denotes |
Viscosalactone B |
T685 |
2771-2780 |
Sentence |
denotes |
Anaferine |
T686 |
2781-2793 |
Sentence |
denotes |
Withasomnine |
T687 |
2794-2801 |
Sentence |
denotes |
Arbidol |
T688 |
2802-2820 |
Sentence |
denotes |
Hydroxychloroquine |
T689 |
2821-2826 |
Sentence |
denotes |
12.4. |
T690 |
2827-2918 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with papain like protease of SARS-CoV-2 (PDB ID: |
T691 |
2919-3013 |
Sentence |
denotes |
6W9C) in comparison to the FDA approved standard reference drugs (Procainamide and Cinacalcet) |
T692 |
3014-3026 |
Sentence |
denotes |
Withaferin A |
T693 |
3027-3040 |
Sentence |
denotes |
Withanolide A |
T694 |
3041-3054 |
Sentence |
denotes |
Withanolide B |
T695 |
3055-3068 |
Sentence |
denotes |
Withanolide D |
T696 |
3069-3082 |
Sentence |
denotes |
Withanolide E |
T697 |
3083-3092 |
Sentence |
denotes |
Withanone |
T698 |
3093-3109 |
Sentence |
denotes |
Viscosalactone B |
T699 |
3110-3119 |
Sentence |
denotes |
Anaferine |
T700 |
3120-3132 |
Sentence |
denotes |
Withasomnine |
T701 |
3133-3145 |
Sentence |
denotes |
Procainamide |
T702 |
3146-3156 |
Sentence |
denotes |
Cinacalcet |
T703 |
3157-3162 |
Sentence |
denotes |
12.5. |
T704 |
3163-3250 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with SARS-CoV main protease/3CL-pro (PBB ID: |
T705 |
3251-3343 |
Sentence |
denotes |
1P9U) in comparison to the FDA approved standard reference drugs (Oberadilol and Poziotinib) |
T706 |
3344-3356 |
Sentence |
denotes |
Withaferin A |
T707 |
3357-3370 |
Sentence |
denotes |
Withanolide A |
T708 |
3371-3384 |
Sentence |
denotes |
Withanolide B |
T709 |
3385-3398 |
Sentence |
denotes |
Withanolide D |
T710 |
3399-3412 |
Sentence |
denotes |
Withanolide E |
T711 |
3413-3422 |
Sentence |
denotes |
Withanone |
T712 |
3423-3439 |
Sentence |
denotes |
Viscosalactone B |
T713 |
3440-3449 |
Sentence |
denotes |
Anaferine |
T714 |
3450-3462 |
Sentence |
denotes |
Withasomnine |
T715 |
3463-3473 |
Sentence |
denotes |
Oberadilol |
T716 |
3474-3484 |
Sentence |
denotes |
Poziotinib |
T717 |
3485-3490 |
Sentence |
denotes |
12.6. |
T718 |
3491-3580 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with SARS-CoV-2 main protease/3CL-pro (PDB ID: |
T719 |
3581-3673 |
Sentence |
denotes |
6LU7) in comparison to the FDA approved standard reference drugs (Oberadilol and Poziotinib) |
T720 |
3674-3686 |
Sentence |
denotes |
Withaferin A |
T721 |
3687-3700 |
Sentence |
denotes |
Withanolide A |
T722 |
3701-3714 |
Sentence |
denotes |
Withanolide B |
T723 |
3715-3728 |
Sentence |
denotes |
Withanolide D |
T724 |
3729-3742 |
Sentence |
denotes |
Withanolide E |
T725 |
3743-3752 |
Sentence |
denotes |
Withanone |
T726 |
3753-3769 |
Sentence |
denotes |
Viscosalactone B |
T727 |
3770-3779 |
Sentence |
denotes |
Anaferine |
T728 |
3780-3792 |
Sentence |
denotes |
Withasomnine |
T729 |
3793-3803 |
Sentence |
denotes |
Oberadilol |
T730 |
3804-3814 |
Sentence |
denotes |
Poziotinib |
T731 |
3815-3820 |
Sentence |
denotes |
12.7. |
T732 |
3821-3915 |
Sentence |
denotes |
Best docking poses of WS phytoconstituents with Nsp-10/Nsp-16 complex from SARS-CoV-2 (PDB ID: |
T733 |
3916-4014 |
Sentence |
denotes |
6W75) in comparison to the FDA approved standard reference drugs (Losartan and Hydroxychloroquine) |
T734 |
4015-4027 |
Sentence |
denotes |
Withaferin A |
T735 |
4028-4041 |
Sentence |
denotes |
Withanolide A |
T736 |
4042-4055 |
Sentence |
denotes |
Withanolide B |
T737 |
4056-4069 |
Sentence |
denotes |
Withanolide D |
T738 |
4070-4083 |
Sentence |
denotes |
Withanolide E |
T739 |
4084-4093 |
Sentence |
denotes |
Withanone |
T740 |
4094-4110 |
Sentence |
denotes |
Viscosalactone B |
T741 |
4111-4120 |
Sentence |
denotes |
Anaferine |
T742 |
4121-4133 |
Sentence |
denotes |
Withasomnine |
T743 |
4134-4142 |
Sentence |
denotes |
Losartan |
T744 |
4143-4161 |
Sentence |
denotes |
Hydroxychloroquine |
T745 |
4163-4167 |
Sentence |
denotes |
3.4. |
T746 |
4169-4281 |
Sentence |
denotes |
Bioavailability radar and score as parameters for analysis of pharmacokinetic properties of WS phytoconstituents |
T747 |
4282-4406 |
Sentence |
denotes |
Pharmacokinetics and pharmacodynamics are two interlinked terms in drug development having a mutual influence on each other. |
T748 |
4407-4519 |
Sentence |
denotes |
Bioavailability radar offers a first glimpse into the pharmaceutical properties of a prospective drug candidate. |
T749 |
4520-4834 |
Sentence |
denotes |
By convention, the pink area represents the optimal biological range for each physiochemical property including lipophilicity (XLOGP3 range 0.7–5.0), size (MW range 150–500), polarity (TPSA range 20–130 Å2), solubility (log S ≤ 6), saturation (fraction of carbons in sp3 hybridization ≤0.25), and flexibility (≤9). |
T750 |
4835-5039 |
Sentence |
denotes |
The Abbot Bioavailability Score62 is identical, but attempts to determine whether a compound is likely to have oral bioavailability score of at least 10% in rats and/or Caco-2 permeability (Martin, 2005). |
T751 |
5040-5216 |
Sentence |
denotes |
As is evident from Figure 2A and B, all withanolides from WS exhibited a significant bioavailability radar and score as comparable to the standard reference FDA-approved drugs. |
T752 |
5217-5420 |
Sentence |
denotes |
Figure 2. (A) Bioavailability radar and score prediction of WS phytoconstituents using SwissADME. (B) Bioavailability radar and score prediction of FDA–approved reference standard drugs using SwissADME. |
T753 |
5422-5426 |
Sentence |
denotes |
3.5. |
T754 |
5428-5477 |
Sentence |
denotes |
Druglikeness and Bioactivity score (BAS) analysis |
T755 |
5478-5652 |
Sentence |
denotes |
Biological targets of prospective drug candidates can be classified into ion channels, proteases, kinases, G-protein coupled receptors (GPCRs), nuclear receptors and enzymes. |
T756 |
5653-5765 |
Sentence |
denotes |
The BAS of WS phytoconstituents was determined using web-based software Molinspiration (www.molinspiration.com). |
T757 |
5766-6010 |
Sentence |
denotes |
As a general rule, it is known that if the BAS > 0.0, then the drug candidate is physiologically active; if it is in the range −5.0 to 0.0; then the drug candidate is moderately active, and if the BAS< −5.0, then the drug candidate is inactive. |
T758 |
6011-6138 |
Sentence |
denotes |
It is evident from Table 13, that most of the WS phytoconstituents had positive values with respect to the following receptors. |
T759 |
6140-6146 |
Sentence |
denotes |
3.5.1. |
T760 |
6148-6163 |
Sentence |
denotes |
As GPCR ligands |