LitCovid-sentences  

PMC:7755033 / 76565-82344 JSONTXT 2 Projects

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Id Subject Object Predicate Lexical cue
T753 0-4 Sentence denotes 3.5.
T754 6-55 Sentence denotes Druglikeness and Bioactivity score (BAS) analysis
T755 56-230 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 231-343 Sentence denotes The BAS of WS phytoconstituents was determined using web-based software Molinspiration (www.molinspiration.com).
T757 344-588 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 589-716 Sentence denotes It is evident from Table 13, that most of the WS phytoconstituents had positive values with respect to the following receptors.
T759 718-724 Sentence denotes 3.5.1.
T760 726-741 Sentence denotes As GPCR ligands
T761 742-875 Sentence denotes All WS phytoconstituents were active except withanolide E, anaferine and withasomnine which were predicted to be moderatively active.
T762 876-1015 Sentence denotes Most of the reference drugs also had positive values for GPCR except procainamide and arbidol which were predicted to be moderately active.
T763 1017-1023 Sentence denotes 3.5.2.
T764 1025-1032 Sentence denotes As ICMs
T765 1033-1138 Sentence denotes All WS phytoconstituents had positive values except withasomnine which was found to be moderately active.
T766 1139-1328 Sentence denotes Standard reference drugs losartan, cinacalcet, hydroxychloroquine, oberadilol and poziotinib were all found to be active whereas procainamide and arbidol were found to be moderately active.
T767 1330-1336 Sentence denotes 3.5.3.
T768 1338-1344 Sentence denotes As KIs
T769 1345-1454 Sentence denotes All WS phytoconstituents displayed moderate activity except withasomnine that displayed significant activity.
T770 1455-1640 Sentence denotes Standard reference drugs losartan, hydroxychloroquine and poziotinib were found to be active whereas procainamide, cinacalcet, arbidol and oberadilol were found to be moderately active.
T771 1642-1648 Sentence denotes 3.5.4.
T772 1650-1657 Sentence denotes As NRLs
T773 1658-1834 Sentence denotes Withaferin A, withanolides A, B, D and E, withanone and viscosalactone B possessed significant BAS scores whereas anaferine and withasomnine were found to be moderately active.
T774 1835-1915 Sentence denotes All standard reference drugs were predicted to have moderate BAS scores as NRLs.
T775 1917-1923 Sentence denotes 3.5.5.
T776 1925-1931 Sentence denotes As PIs
T777 1932-2079 Sentence denotes Withaferin A, withanolides A, B, D and E, withanone and viscosalactone B had positive BAS scores indicating their potential as protease inhibitors.
T778 2080-2186 Sentence denotes On the other hand, anaferine and withasomnine were found to have moderate activity as protease inhibitors.
T779 2187-2331 Sentence denotes Interestingly, most withanolides especially withanolide B and withanolide A showed potent binding to papain like protease of SARS-CoV-2 (PDB ID:
T780 2332-2429 Sentence denotes 6W9C), SARS-CoV 3CL-pro main protease (PDB ID: IP9U) and SARS-CoV-2 Nsp10/Nsp-16 complex (PDB ID:
T781 2430-2502 Sentence denotes 6W75) thus supporting their role as potential viral protease inhibitors.
T782 2503-2729 Sentence denotes On the other hand, losartan, cinacalcet and hydroxychloroquine also displayed positive values as protease inhibitors whereas procainamide, arbidol, oberadilol and poziotinib displayed moderate potential as protease inhibitors.
T783 2731-2737 Sentence denotes 3.5.6.
T784 2739-2745 Sentence denotes As EIs
T785 2746-2995 Sentence denotes Most of the WS phytoconstituents including Withaferin A, withanolides A, B, D and E, withanone, viscosalactone B and anaferine had positive BAS scores indicating their potential as enzyme inhibitors whereas withasomnine displayed moderate potential.
T786 2996-3351 Sentence denotes This observation was further validated by the fact that most of the phytoconstituents including Withaferin A, withanolides A, B, D and E, viscosalactone B and anaferine showed potent binding to human ACE2 receptor in the nanomolar range which was about 1000× times greater than the binding of known standard reference drugs arbidol and losartan (Table 4).
T787 3352-3545 Sentence denotes This finding lends support for targeted use of withanolides from WS as SARS-CoV-2 entry blocking agents by virtue of their preferential binding to human ACE2, thereby blocking or inhibiting it.
T788 3546-3734 Sentence denotes Losartan, cinacalcet, hydroxychloroquine, oberadilol and poziotinib also displayed significant potential as enzyme inhibitors whereas procainamide and arbidol displayed moderate potential.
T789 3735-3845 Sentence denotes Druglikeness of a compound can be predicted by comparing its structural features with those of marketed drugs.
T790 3846-3981 Sentence denotes All WS phytoconstituents showed molar lipophilicity (cLog P) <5 thereby indicating good permeability across cell membranes (Figure 2A).
T791 3982-4171 Sentence denotes Withaferin A, withanolide D, viscosalactone B and withasomnine had positive values of druglikeness which indicated that these compounds contain fragments that are present in marketed drugs.
T792 4172-4311 Sentence denotes Out of the standard reference drugs, procainamide, hydroxychloroquine and oberadilol exhibited positive scores for druglikeness (Table 14).
T793 4312-4321 Sentence denotes Table 13.
T794 4323-4518 Sentence denotes Bioactivity scores and Druglikeness of WS phytoconstituents versus FDA-approved standard reference drugs (Losartan, Procainamide, Cinacalcet, Arbidol, Hydroxychloroquine, Oberadilol, Poziotinib).
T795 4519-4521 Sentence denotes S.
T796 4522-4525 Sentence denotes No.
T797 4527-4567 Sentence denotes Ligands Parameters of bioactivity score
T798 4568-4712 Sentence denotes GPCR ligand Ion channel modulator (ICM) Kinase inhibitor (KI) Nuclear receptor ligand (NRL) Protease inhibitor (PI) Enzymeinhibitor (EI)  
T799 4713-4738 Sentence denotes                  
T800 4739-4741 Sentence denotes 1.
T801 4743-4795 Sentence denotes Withaferin A 0.07 0.14 –0.49 0.76 0.15 0.94  
T802 4796-4798 Sentence denotes 2.
T803 4800-4853 Sentence denotes Withanolide A 0.04 0.32 –0.43 0.71 0.15 0.86  
T804 4854-4856 Sentence denotes 3.
T805 4858-4911 Sentence denotes Withanolide B 0.07 0.24 –0.47 0.79 0.15 0.76  
T806 4912-4914 Sentence denotes 4.
T807 4916-4969 Sentence denotes Withanolide D 0.05 0.30 –0.50 0.73 0.16 1.07  
T808 4970-4972 Sentence denotes 5.
T809 4974-5028 Sentence denotes Withanolide E –0.70 0.16 –0.50 0.61 0.06 0.89  
T810 5029-5031 Sentence denotes 6.
T811 5033-5082 Sentence denotes Withanone 0.00 0.27 –0.38 0.71 0.12 0.78  
T812 5083-5085 Sentence denotes 7.
T813 5087-5143 Sentence denotes Viscosalactone B 0.03 0.04 –0.51 0.78 0.19 0.84  
T814 5144-5146 Sentence denotes 8.
T815 5148-5200 Sentence denotes Anaferine –0.08 0.17 –0.60 –0.58 –0.14 0.08  
T816 5201-5203 Sentence denotes 9.
T817 5205-5261 Sentence denotes Withasomnine –0.49 –0.43 0.58 –0.10 –0.58 –0.17  
T818 5262-5265 Sentence denotes 10.
T819 5267-5314 Sentence denotes Losartan 1.06 0.16 0.03 0.01 0.33 0.44  
T820 5315-5318 Sentence denotes 11.
T821 5320-5376 Sentence denotes Procainamide –0.09 0.01 –0.10 –0.70 –0.20 –0.04  
T822 5377-5380 Sentence denotes 12.
T823 5382-5433 Sentence denotes Cinacalcet 0.22 0.15 –0.0.8 0.00 0.17 0.02  
T824 5434-5437 Sentence denotes 13.
T825 5439-5491 Sentence denotes Arbidol –0.19 –0.44 –0.39 –0.34 –0.46 –0.07  
T826 5492-5495 Sentence denotes 14.
T827 5497-5555 Sentence denotes Hydroxychloroquine 0.35 0.30 0.44 –0.12 0.12 0.15  
T828 5556-5559 Sentence denotes 15.
T829 5561-5614 Sentence denotes Oberadilol 0.04 –0.47 –0.43 –0.37 –0.02 0.02  
T830 5615-5618 Sentence denotes 16.
T831 5620-5672 Sentence denotes Poziotinib 0.04 –0.17 0.53 –0.35 –0.27 0.01  
T832 5673-5686 Sentence denotes Rule: BAS >0:
T833 5687-5694 Sentence denotes Active;
T834 5695-5708 Sentence denotes BAS –5.0–0.0:
T835 5709-5759 Sentence denotes Moderately active, moderately active and inactive.
T836 5760-5769 Sentence denotes BAS ≤5.0:
T837 5770-5779 Sentence denotes Inactive;