LitCovid-sentences  

PMC:7441777 / 8777-19310 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T60 0-2 Sentence denotes 2.
T61 4-25 Sentence denotes Materials and methods
T62 27-31 Sentence denotes 2.1.
T63 33-58 Sentence denotes Molecular docking studies
T64 60-66 Sentence denotes 2.1.1.
T65 68-88 Sentence denotes Protein preparations
T66 89-138 Sentence denotes The crystal structure of SARS-CoV-2 RdRp (PDB ID:
T67 139-241 Sentence denotes 6M71) (Yan et al., 2020) was retrieved from the protein databank (www.rcsb.org) (Berman et al., 2000).
T68 242-404 Sentence denotes The crystal structure was prepared individually by adding hydrogen atoms and computing the Gasteiger charge using the AutoDock v4.2 program (Morris et al., 2009).
T69 405-492 Sentence denotes Subsequently, the file was saved as .pdbqt format in preparation for molecular docking.
T70 493-636 Sentence denotes Schematic representation of the work-flow for selecting potential natural polyphenolic inhibitors for the SARS-CoV-2 RdRp is shown in Figure 2.
T71 637-646 Sentence denotes Figure 2.
T72 648-758 Sentence denotes Flow chart of the methodology for shortlisting the best natural polyphenolic inhibitor of the SARS-CoV-2 RdRp.
T73 760-766 Sentence denotes 2.1.2.
T74 768-787 Sentence denotes Ligand preparations
T75 788-1000 Sentence denotes The SDF structures of GTP, remdesivir, and selected hundred polyphenols (see Table S1 in Supplementary Information) were retrieved from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/) (Kim et al., 2019).
T76 1001-1158 Sentence denotes The compounds were converted into PDB format, and conformational energies of all the compounds were minimized by using UCSF Chimera (Pettersen et al., 2004).
T77 1159-1167 Sentence denotes Table 1.
T78 1169-1315 Sentence denotes Binding energy (kcal/mol) of the natural polyphenols along with the control compounds (GTP and remdesivir) against RdRp of the SARS-CoV-2 (PDB ID:
T79 1316-1349 Sentence denotes 6M71) by molecular docking study.
T80 1350-1352 Sentence denotes S.
T81 1353-1356 Sentence denotes No.
T82 1358-1402 Sentence denotes Compound Name Binding energy (kcal/mol) S.
T83 1403-1406 Sentence denotes No.
T84 1408-1448 Sentence denotes Compound Name Binding energy (kcal/mol)
T85 1449-1483 Sentence denotes 1 TF3 −9.9 52 Cyanidin −6.3
T86 1484-1519 Sentence denotes 2 TF2b −9.6 53 Daidzein −6.3
T87 1520-1555 Sentence denotes 3 TF1 −9.6 54 Glycitein −6.3
T88 1556-1590 Sentence denotes 4 TF2a −9.3 55 Wogonin −6.3
T89 1591-1633 Sentence denotes 5 Hesperidin −8.8 56 Phloretin −6.3
T90 1634-1669 Sentence denotes 6 EGCG −7.3 57 Catechin −6.2
T91 1670-1713 Sentence denotes 7 Myricetin −7.2 58 Urolithin B −6.2
T92 1714-1760 Sentence denotes 8 Quercetagetin −7.0 59 Angolensin −6.2
T93 1761-1801 Sentence denotes 9 Quercetin −6.9 60 Pinosylvin −6.2
T94 1802-1844 Sentence denotes 10 Curcumin −6.9 61 Formononetin −6.2
T95 1845-1897 Sentence denotes 11 Dihydrorobinetin −6.8 62 Liquiritigenin −6.2
T96 1898-1936 Sentence denotes 12 Peonidin −6.8 63 Prunetin −6.2
T97 1937-1975 Sentence denotes 13 Fisetin −6.8 64 Alpinetin −6.2
T98 1976-2018 Sentence denotes 14 Robinetin −6.7 65 Biochanin A −6.2
T99 2019-2069 Sentence denotes 15 5-Deoxygalangin −6.7 66 Rhapontigenin −6.1
T100 2070-2111 Sentence denotes 16 Kaempferol −6.7 67 Genistein −6.1
T101 2112-2153 Sentence denotes 17 Scutellarein −6.7 68 Chrysin −6.1
T102 2154-2207 Sentence denotes 18 (-)-Epicatechin −6.7 69 6-Hydroxyflavone −6.1
T103 2208-2243 Sentence denotes 19 Purpurin −6.7 70 Equol −6.1
T104 2244-2289 Sentence denotes 20 Isorhamnetin −6.7 71 Piceatannol −6.1
T105 2290-2336 Sentence denotes 21 Tricetin −6.6 72 Isorhapontigenin −6.0
T106 2337-2380 Sentence denotes 22 Gossypetin −6.6 73 Resveratrol −5.8
T107 2381-2423 Sentence denotes 23 Norathyriol −6.6 74 Danshensu −5.7
T108 2424-2463 Sentence denotes 24 Coumestrol −6.6 75 Eugenin −5.6
T109 2464-2512 Sentence denotes 25 Isosakuranetin −6.6 76 Sinapic acid −5.5
T110 2513-2564 Sentence denotes 26 Pectolinarigenin −6.6 77 Pterostilbene −5.5
T111 2565-2609 Sentence denotes 27 Tangeritin −6.6 78 Ferulic acid −5.4
T112 2610-2653 Sentence denotes 28 Nobiletin −6.6 79 Caffeic acid −5.4
T113 2654-2701 Sentence denotes 29 Pratensein −6.6 80 Isoferulic acid −5.4
T114 2702-2753 Sentence denotes 30 Hispidulin −6.6 81 Dihydrocaffeic acid −5.4
T115 2754-2798 Sentence denotes 31 Baicalein −6.5 82 Gentisic acid −5.3
T116 2799-2839 Sentence denotes 32 Apigenin −6.5 83 Pyrogallol −5.3
T117 2840-2889 Sentence denotes 33 Morin −6.5 84 4-Hydroxycinnamic acid −5.2
T118 2890-2938 Sentence denotes 34 Urolithin A −6.5 85 Resacetophenone −5.2
T119 2939-2984 Sentence denotes 35 Acacetin −6.5 86 Salicyclic acid −5.1
T120 2985-3032 Sentence denotes 36 Pelargonidin −6.5 87 Syringic acid −5.1
T121 3033-3083 Sentence denotes 37 Irilone −6.5 88 2-Hydroxybenzoic acid −5.1
T122 3084-3127 Sentence denotes 38 Naringenin −6.5 89 Gallic acid −5.0
T123 3128-3182 Sentence denotes 39 Pinocembrin −6.5 90 3-Hydroxybenzoic acid −5.0
T124 3183-3237 Sentence denotes 40 Kaempferide −6.5 91 4-Hydroxybenzoic acid −5.0
T125 3238-3276 Sentence denotes 41 Malvidin −6.5 92 Vanillin −5.0
T126 3277-3322 Sentence denotes 42 Luteolin −6.4 93 p-Coumeric acid −4.9
T127 3323-3367 Sentence denotes 43 Dalbergin −6.4 94 Vanillic acid −4.8
T128 3368-3403 Sentence denotes 44 Butein −6.4 95 Paeonol −4.8
T129 3404-3455 Sentence denotes 45 Biochanin A (1-) −6.4 96 Cinnamic acid −4.7
T130 3456-3503 Sentence denotes 46 Fustin −6.4 97 Protocatechuic acid −4.6
T131 3504-3555 Sentence denotes 47 5-Hydroxyflavone −6.4 98 4-Ethylphenol −4.5
T132 3556-3597 Sentence denotes 48 Pinostrobin −6.4 99 Catechol −4.5
T133 3598-3639 Sentence denotes 49 Pinobanksin −6.4 100 Tyrosol −4.5
T134 3640-3678 Sentence denotes 50 Datiscetin −6.3 101 GTP −7.9
T135 3679-3722 Sentence denotes 51 Galangin −6.3 102 Remdesivir −7.7
T136 3724-3730 Sentence denotes 2.1.3.
T137 3732-3767 Sentence denotes Docking studies using AutoDock Vina
T138 3768-3950 Sentence denotes The energy-minimized structure of all the natural polyphenols, remdesivir, and GTP were docked with the receptor (RdRp of SARS-CoV-2) using AutoDock Vina 1.1.2 (Trott & Olson, 2010).
T139 3951-4139 Sentence denotes The ligand files were further saved in PDBQT file format, a modified PDB format containing atomic charges, atom type definitions for ligands, and topological information (rotatable bonds).
T140 4140-4263 Sentence denotes A grid box (30 Å × 30 Å × 30 Å) centered at (121, 120, 125) Å for the SARS-CoV-2 RdRp, was used in the docking experiments.
T141 4264-4353 Sentence denotes After the receptor-ligand preparation, docking runs were started from the command prompt.
T142 4354-4478 Sentence denotes The lowest binding energy and best-docked conformation were considered as the ligand molecule with maximum binding affinity.
T143 4480-4486 Sentence denotes 2.1.4.
T144 4488-4515 Sentence denotes Protein-ligand interactions
T145 4516-4699 Sentence denotes LigPlot+ was used to investigate protein-ligand interactions for a given .pdb file containing the docked conformation and also the final simulated conformation (Wallace et al., 1995).
T146 4700-4795 Sentence denotes The LigPlot+ program self-generated schematic 2D representations of protein-ligand interaction.
T147 4796-4949 Sentence denotes The output file represents the intermolecular interactions and their strengths, including hydrogen bonds, hydrophobic contacts, and atom accessibilities.
T148 4950-5082 Sentence denotes H-bonds are shown in green dotted lines, whereas residues involved in hydrophobic interaction are represented in the red semicircle.
T149 5084-5088 Sentence denotes 2.2.
T150 5090-5120 Sentence denotes Molecular dynamics simulations
T151 5121-5397 Sentence denotes All-atom molecular dynamics (MD) simulations were performed on the best eight selected plant-derived natural polyphenols obtained from the molecular docking study along with remdesivir, a well-known RdRp inhibitor, for studying thermodynamic stability of the docked structure.
T152 5398-5443 Sentence denotes The pmemd.cuda module in AMBER18 (Case et al.
T153 5444-5565 Sentence denotes 2018) was used for conducting MD simulations, and all simulations were performed utilizing the graphics card, RTX 2080Ti.
T154 5566-5709 Sentence denotes We adopted the same protocol that was used in our earlier studies (Jonniya et al., 2019; Sk, Roy, Jonniya, et al., 2020; Sk, Roy, & Kar, 2020).
T155 5710-5855 Sentence denotes The receptor and small molecules were described by the Amber ff14SB (Maier et al., 2015) and GAFF2 (Wang et al., 2004) force field, respectively.
T156 5856-5989 Sentence denotes Ligands were assigned the AM1-BCC (Jakalian et al., 2002) atomic charges calculated using the antechamber (Wang et al., 2001) module.
T157 5990-6155 Sentence denotes The complexes were then solvated using an explicit TIP3P (Price & Brooks III, 2004) water model, and nearly 38124 water molecules were needed to solvate each system.
T158 6156-6251 Sentence denotes Subsequently, all solvated systems were neutralized by adding an appropriate number of Na+ ion.
T159 6252-6360 Sentence denotes All bond lengths, including hydrogen atoms, were constrained by the SHAKE algorithm (Kräutler et al., 2001).
T160 6361-6403 Sentence denotes This allows the usage of a 2 fs time-step.
T161 6404-6568 Sentence denotes The non-bonded cut-off was set to 8 Å and the long range electrostatic interactions were evaluated using the particle-mesh Ewald (PME) (Darden et al., 1993) method.
T162 6569-6696 Sentence denotes The temperature was kept at 300 K using the Langevin thermostat (Loncharich et al., 1992) with a collision frequency of 2 ps−1.
T163 6697-6802 Sentence denotes The system pressure was controlled by Berendsen’s Barostat (Berendsen et al., 1984) and fixed at 1.0 bar.
T164 6803-6853 Sentence denotes We used a time-step of 2.0 fs for all simulations.
T165 6854-6898 Sentence denotes Briefly, we used two stages of minimization.
T166 6899-7173 Sentence denotes Firstly, each complex was optimized by 500 steps of steepest descent followed by another 500 steps of conjugate gradient minimization, keeping all atoms of the complex restrained to their initial coordinate with a weak harmonic potential (force constant 2.0 kcal mol−1 Å−2).
T167 7174-7394 Sentence denotes The second stage of minimization was carried out without any restraints by performing 100 steps of steepest descent, followed by another 900 steps of conjugate gradient minimization to remove any residual steric clashes.
T168 7395-7551 Sentence denotes Subsequently, all systems were gradually heated from 0 K to 300 K at the NVT ensemble with a force constant of 2.0 kcal mol−1Å−2 acting on all solute atoms.
T169 7552-7626 Sentence denotes Next, 1.0 ns equilibration MD phase was carried out without any restraint.
T170 7627-7720 Sentence denotes Finally, we performed 150 ns production simulations for all four systems at the NPT ensemble.
T171 7721-7902 Sentence denotes Overall, we accumulated 15000 conformations for each simulation, and we used 500 snapshots from the last 50 ns trajectories for binding affinity estimation using the MM-PBSA scheme.
T172 7903-8009 Sentence denotes The trajectory analysis was done by the AmberTools19 CPPTRAJ (Roe & Cheatham III, 2013) module of Amber18.
T173 8011-8015 Sentence denotes 2.3.
T174 8017-8080 Sentence denotes Molecular mechanics Poisson-Boltzmann surface area calculations
T175 8081-8507 Sentence denotes The binding affinity of EGCG, TF1, TF3, TF2b, TF2a, hesperidin, myricetin, quercetagetin, and remdesivir against the SARS-CoV-2 RdRp, were calculated by the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methodology (Jonniya & Kar, 2020; Kar, Seel, et al., 2007; Kar, Wei, et al., 2007; Kar et al., 2011; 2013; Kar & Knecht, 2012a, 2012b, 2012c, 2012d; Kollman et al., 2000; Roy et al., 2020; Wang et al., 2006).
T176 8508-8789 Sentence denotes The MM-PBSA scheme can briefly be described as follows: (1) ΔGbind=ΔH−TΔS≈ΔEMM+ΔGsolv−TΔS (2) ΔEMM=ΔEinternal+ΔEelec+ΔEvdW (3) ΔGsolv=ΔGpol+ΔGnp where ΔEMM, ΔGsolv, TΔS are the changes in molecular mechanical energy, solvation free energy, and conformational entropy, respectively.
T177 8790-9055 Sentence denotes Further, molecular mechanical energy is composed of ΔEinternal (bond, dihedral, and angle), ΔEelec (electrostatic) and ΔEvdW (van der Waals) and the change in desolvation free energy is composed of polar solvation (ΔGpol) and non-polar solvation free energy (ΔGnp).
T178 9056-9141 Sentence denotes The polar solvation free energy, ΔGpol, was calculated by the pbsa module of AMBER18.
T179 9142-9230 Sentence denotes Due to the high computational cost, we neglect the configurational entropy calculations.
T180 9231-9499 Sentence denotes Further, to understand the polyphenol-protein interaction more closely, the interaction energy was decomposed into the contributions from each residue of the protein by using the molecular mechanics generalized Born surface area (MM-GBSA) scheme (Gohlke et al., 2003).
T181 9501-9505 Sentence denotes 2.4.
T182 9507-9520 Sentence denotes ADMET studies
T183 9521-9644 Sentence denotes The in-silico pharmacological studies of EGCG, TF2a, TF2b, TF3, and remdesivir were predicted based on their ADMET profile.
T184 9645-9834 Sentence denotes The ADMET studies (absorption, distribution, metabolism, elimination, and toxicity) were predicted using the pkCSM tool (http://biosig.unimelb.edu.au/pkcsm/prediction) (Pires et al., 2015).
T185 9835-9981 Sentence denotes The canonical SMILE molecular structures of the above-mentioned compounds were retrieved from the PubChem database (www.pubchem.ncbi.nlm.nih.gov).
T186 9983-9987 Sentence denotes 2.5.
T187 9989-10016 Sentence denotes Molecular target prediction
T188 10017-10093 Sentence denotes Natural compounds interact with a large number of proteins, enzymes, lipids.
T189 10094-10194 Sentence denotes This interaction plays a crucial role in elucidating the molecular mechanism of the small molecules.
T190 10195-10290 Sentence denotes So, it is important to identify the molecular targets for new molecules (Gfeller et al., 2014).
T191 10291-10533 Sentence denotes Swiss Target Prediction website (http://www.swisstargetprediction.ch/index.php) was logged on, and canonical SMILE molecular structures of remdesivir, EGCG, TF2a, TF2b, and TF3 were entered in the search bar option, and results were analyzed.