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LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T1 2275-2284 Phenotype denotes pneumonia http://purl.obolibrary.org/obo/HP_0002090
T2 2390-2399 Phenotype denotes pneumonia http://purl.obolibrary.org/obo/HP_0002090
T3 2940-2949 Phenotype denotes pneumonia http://purl.obolibrary.org/obo/HP_0002090
T4 2955-2974 Phenotype denotes respiratory failure http://purl.obolibrary.org/obo/HP_0002878
T5 4707-4713 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664
T6 28043-28049 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T1 0-111 Sentence denotes Virtual screening of curcumin and its analogs against the spike surface glycoprotein of SARS-CoV-2 and SARS-CoV
T2 112-114 Sentence denotes A.
T3 115-127 Sentence denotes Patel et al.
T4 128-174 Sentence denotes Journal of Biomolecular Structure and Dynamics
T5 176-184 Sentence denotes Abstract
T6 185-193 Sentence denotes Abstract
T7 194-286 Sentence denotes COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China.
T8 287-416 Sentence denotes The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74% identity and use similar mechanisms to gain entry into the cell.
T9 417-558 Sentence denotes Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2).
T10 559-668 Sentence denotes Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle.
T11 669-773 Sentence denotes The crystal structure of the SARS-CoV (6CRV: full length S protein) and SARS-CoV-2 Spike proteins (6M0J:
T12 774-862 Sentence denotes Receptor binding domain, RBD) was used to determine potential small molecule inhibitors.
T13 863-977 Sentence denotes Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties.
T14 978-1178 Sentence denotes In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby, viral entry.
T15 1179-1325 Sentence denotes The curcumin and its derivatives displayed binding energies, ΔG, ranging from −10.98 to −5.12 kcal/mol (6CRV) and −10.01 to −5.33 kcal/mol (6M0J).
T16 1326-1446 Sentence denotes The least binding energy was seen in bis-demethoxycurcumin with: ΔG = −10.98 kcal/mol (6CRV) and −10.01 kcal/mol (6M0J).
T17 1447-1625 Sentence denotes A good binding energy, drug likeness and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors.
T18 1626-1737 Sentence denotes However, further research is necessary to investigate the ability of these compounds as viral entry inhibitors.
T19 1738-1766 Sentence denotes Communicated by Ramaswamy H.
T20 1767-1772 Sentence denotes Sarma
T21 1774-1786 Sentence denotes Introduction
T22 1787-1898 Sentence denotes Coronaviruses are enveloped positive-sense single stranded RNA viruses that belong to the family coronaviridae.
T23 1899-1997 Sentence denotes They usually infect birds and mammals and cause mild respiratory diseases (Kahn & McIntosh, 2005).
T24 1998-2195 Sentence denotes However, in the recent past, these viruses have caused lethal endemics such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) endemics (Kahn & McIntosh, 2005).
T25 2196-2324 Sentence denotes In December 2019, Wuhan city in China became the centre of a surge in cases of pneumonia by an unknown cause (Zhu et al., 2020).
T26 2325-2600 Sentence denotes A novel corona virus, called SARS-CoV-2, was isolated from these pneumonia patients in January 2020 and the disease was called the Coronavirus disease 2019 (COVID-19) by the World Health Organization in February, 2020 (Gorbalenya et. al, 2020; Jiang et al., 2020; Who, 2020).
T27 2601-2812 Sentence denotes Even though the epidemic may have started from a zoonotic transmission in a seafood market, that also sold wild animals, it became clear that this disease was transmitted from person to person (Li et al., 2020).
T28 2813-3049 Sentence denotes The clinical characteristics of this disease are broad, constituting asymptomatic infections, mild respiratory disease, severe pneumonia with respiratory failure and even death (Chen et al., 2020; Huang et al., 2020; Wang et al., 2020).
T29 3050-3293 Sentence denotes The COVID-19 pandemic poses a significant challenge to global public health (Phelan et al., 2020), appealing for the development of safe and successful prophylactics and therapies against infection of its causative agent, the SARS-CoV-2 virus.
T30 3294-3420 Sentence denotes SARS-CoV-2 has a genome of ∼30 kilobases, which codes for multiple structural and non-structural proteins (Chan et al., 2020).
T31 3421-3610 Sentence denotes The structural proteins, present on the surface of the mature virion, include the spike protein, the membrane protein, the envelope protein and the nucleocapsid protein (Chan et al., 2020).
T32 3611-3830 Sentence denotes The Spike protein, of the beta coronaviruses SARS-CoV-2 and SARS-CoV, enables the attachment of the virus to the cells of the lower respiratory tract of humans to gain entry into the lung tissue (Hoffmann et al., 2020).
T33 3831-3995 Sentence denotes Apart from attachment, the spike glycoprotein also appears to play a role in fusion and entry of the virus into the host (Chen et al., 2020; Hoffmann et al., 2020).
T34 3996-4180 Sentence denotes The spike protein, of the novel coronavirus, utilizes the SARS-CoV receptor, ACE2 for entry (Chen et al., 2020) and is primed by the cellular protease, TMPRSS2 (Hoffmann et al., 2020).
T35 4181-4310 Sentence denotes A serine protease inhibitor, which can act on TMPRSS2, has been shown to inhibit novel coronavirus entry (Hoffmann et al., 2020).
T36 4311-4524 Sentence denotes Therefore, the spike protein of the novel coronavirus is a good drug target and identifying small molecules that bind to S protein would inhibit viral recognition of host cells and disrupt viral-host interactions.
T37 4525-4823 Sentence denotes Curcumin, a naturally occurring phytochemical and principal component of Curcuma longa, has exhibited broad pharmacological properties including antioxidant, anti-inflammatory, anti-cancer and anti-viral effects (Khor et al., 2019; Kocaadam & Şanlier, 2017; Lal et al., 2016; Wiggers et al., 2017).
T38 4824-4960 Sentence denotes Curcumin and its derivatives, due to its rich conventional medicinal interest, has undergone comprehensive in vitro and in vivo studies.
T39 4961-5101 Sentence denotes It has, therefore, been associated with more than 100 cellular targets, including cytokines, proteins, transcription factors, and receptors.
T40 5102-5316 Sentence denotes Previous studies have shown the potential of curcumin as a treatment against Influenza A virus infection, by an effect mediated by modulating immune response to prevent injury to the lung tissue (Han et al., 2018).
T41 5317-5445 Sentence denotes Curcumin has also been shown to have anti neuraminidase (NA) activity for the influenza virus NA protein (Richart et al., 2018).
T42 5446-5614 Sentence denotes Therefore, in the present study, curcumin and its derivatives were docked onto the spike protein of the SARS-CoV and the SARS-CoV-2 to predict the binding interactions.
T43 5615-5731 Sentence denotes We found that curcumin and few of its derivatives showed promising results to be potential spike protein inhibitors.
T44 5732-5893 Sentence denotes One of the derivatives, bis-demethoxycurcumin, showed the best binding affinity to the spike protein of both the SARS-CoV and the novel corona virus, SARS-CoV-2.
T45 5894-6043 Sentence denotes The possibility for few of the curcumin derivatives, that showed good binding affinity, could be tested for further therapeutic use against COVID-19.
T46 6045-6065 Sentence denotes Experimental section
T47 6067-6084 Sentence denotes Sequence analysis
T48 6085-6197 Sentence denotes The sequences of the SARS-CoV-2 and SARS-CoV were downloaded from National Center for Biotechnology Information.
T49 6198-6366 Sentence denotes Multiple sequence analysis and pairwise sequence identity was determined using the Clustal Omega server at the European Bioinformatics Institute (Sievers et al., 2011).
T50 6368-6398 Sentence denotes Preparation of coordinate file
T51 6399-6480 Sentence denotes The X-ray crystal structure of spike surface glycoprotein of SARS-CoV (PDB entry:
T52 6481-6590 Sentence denotes 6CRV, resolution = 3.2 Å) and co-crystallized structure of SARS-CoV-2 RBD with human ACE2 Protein (PDB entry:
T53 6591-6681 Sentence denotes 6M0J, resolution = 2.45 Å) was retrieved from Protein Data Bank (https:/www.rscb.org/pdb).
T54 6682-7046 Sentence denotes The protein structure was prepared using the Discovery Studio Visualizer (version 3.1) and AutoDock Tools (ADT; version 1.5.4) through different steps viz. removal of water molecules and co-crystallized ligand, addition of missing hydrogen atoms, addition of Gasteiger-Marsili and Kollman charges, merging of non-polar hydrogens, and assignment of rotatable bonds.
T55 7047-7113 Sentence denotes The file was then saved in pdbqt file format for further analysis.
T56 7115-7137 Sentence denotes Preparation of ligands
T57 7138-7271 Sentence denotes The chemical structures of curcumin derivatives were constructed using Chem3D 15.0 module of ChemOffice 15.0 and saved in PDB format.
T58 7272-7441 Sentence denotes The structures were optimized using “Prepare Ligands” in the AutoDock 4.2, flexible torsions were assigned and the acyclic dihedral angles were allowed to rotate freely.
T59 7442-7508 Sentence denotes The file was then saved as pdbqt file format for further analysis.
T60 7510-7527 Sentence denotes Molecular docking
T61 7528-7709 Sentence denotes Molecular docking simulations were conducted on the curcumin derivatives using the AutoDock 4.2 to get insight into their binding preferences within the active site of the receptor.
T62 7710-7831 Sentence denotes The molecular docking simulations were performed on the PC based machines running on Windows 7 (x86) as operating system.
T63 7832-8029 Sentence denotes The software included MGL tools 1.5.4 based AutoDock 4.2 (www.scripps.edu) which uses Python 2.7 language - Cygwin C:\program (www.cygwin.com) and Python 2.5 (www.python.com) (Morris et al., 2009).
T64 8031-8050 Sentence denotes Docking methodology
T65 8051-8173 Sentence denotes The flexible docking was performed using the refined spike protein of SARS-CoV (6CRV) and RBD domain of SARS-CoV-2 (6M0J).
T66 8174-8277 Sentence denotes The grid maps of the interaction energies of various atom types were pre-calculated using AutoGrid 4.2.
T67 8278-8478 Sentence denotes In each docking for spike surface glycoprotein and spike RBD, a grid box was created using a grid map of 45 × 45 × 45 points, 60 × 60 × 60 points with grid spacing of 0.375 Å and 0.420 Å respectively.
T68 8479-8576 Sentence denotes The grid maps were centred on the corresponding ligand binding site within the protein structure.
T69 8577-8699 Sentence denotes Lamarckian Genetic Algorithm (LGA) was adopted to perform docking simulations using the following default parameters, viz.
T70 8700-9057 Sentence denotes 100 independent runs with step sizes of 0.2 Å for translations and 5 Å for orientations and torsions, an initial population of random individuals with a population size of 150 individuals, a maximum of 2.5 × 106 energy evaluations, maximum number of generations of 27,000; mutation and crossover rates of 0.02 and 0.8 respectively and an elitism value of 1.
T71 9058-9223 Sentence denotes All the computations were carried out on Cygwin and was used to generate both grid parameter file (.gpf file) and docking parameter file (.dpf file) for each ligand.
T72 9224-9379 Sentence denotes The docked conformations of each ligand were ranked into clusters based on the binding energy and the top ranked conformations were used for further study.
T73 9380-9507 Sentence denotes The pose with the lowest ΔG-score was considered the best fitted one and was further analyzed for Ligand-receptor interactions.
T74 9509-9572 Sentence denotes In-silico drug-likeness and pharmacokinetic property prediction
T75 9573-9792 Sentence denotes The in-silico prediction studies were performed, using pkCSM online prediction platforms (Pires et al., 2015), to assess the theoretical pharmacokinetic parameters of the ligands to predict the drug-likeness of ligands.
T76 9793-9981 Sentence denotes The software calculated pharmaceutically relevant properties such as H-bond donor, H-bond acceptor, octanol-water partition coefficient (LogP), surface area, and number of rotatable bonds.
T77 9982-10412 Sentence denotes In addition the ADME parameters of the curcumin analogs such as water solubility, Caco2 permeability, human intestinal absorption, skin permeability, P-glycoprotein I and II inhibition, volume of distribution, fraction of unbound drug, Blood Brain Barrier and CNS permeability, cytochrome P450 (CYP3A4 and CYP2C9 inhibition) inhibition, total clearance, action as renal OCT2 (organic cation transporter 2) substrate were analysed.
T78 10414-10421 Sentence denotes Results
T79 10423-10496 Sentence denotes Sequence alignment of the SARS-CoV-2 and SARS-CoV spike protein sequences
T80 10497-10705 Sentence denotes Prior to performing the docking studies the multiple sequence alignment was carried out for the spike proteins of the novel corona virus, SARS-CoV-2 and the 2002 SARS-CoV (Supplementary Figure 1 and Table 1).
T81 10706-10859 Sentence denotes These results show that there is a very high percentage identity (greater than 99%) among the spike protein of the novel corona virus SARS-CoV-2 strains.
T82 10860-10946 Sentence denotes There was around 74% identity of the SARS-CoV-2 spike proteins with the 2002 SARS-CoV.
T83 10947-11099 Sentence denotes Therefore, the SARS-CoV-2 spike protein is very much closer to SARS-CoV than to the other corona viruses as shown in other studies (Ahmed et al., 2020).
T84 11100-11109 Sentence denotes Figure 1.
T85 11111-11225 Sentence denotes The curcumin and its derivatives which displayed high binding affinity for SARS-CoV-2 and SARS-CoV spike proteins.
T86 11226-11234 Sentence denotes Table 1.
T87 11236-11312 Sentence denotes Percentage identity Matrix of Spike glycoprotein of SARS-CoV-2 and SARS-CoV.
T88 11313-11537 Sentence denotes Indian 1 and 2 (QHS34546.1 and QIA98583.1), Korea (QHZ00379.1), Brazil (QIG55994.1), USA (QHO60594.1), Wuhan (QHD43416.1), Pakistan (QIQ22760.1), Italy (QIA98554.1), Australia (QHR84449.1) are spike proteins from SARS-CoV-2.
T89 11538-11613 Sentence denotes SARS-6CRV is the spike protein from the 2002 SARS-CoV spike protein (6CRV).
T90 11614-11709 Sentence denotes Viral Strain SARS-CoV Indian1 Korea Indian2 Brazil USA Wuhan Pakistan Italy Australia
T91 11710-11786 Sentence denotes SARS-CoV 100 73.75 73.77 73.69 73.77 73.77 73.77 73.77 73.77 73.77
T92 11787-11862 Sentence denotes Indian1 73.75 100 99.84 99.84 99.92 99.92 99.92 99.92 99.92 99.84
T93 11863-11936 Sentence denotes Korea 73.77 99.84 100 99.84 99.92 99.92 99.92 99.92 99.92 99.84
T94 11937-12012 Sentence denotes Indian2 73.69 99.84 99.84 100 99.92 99.92 99.92 99.92 99.92 99.84
T95 12013-12079 Sentence denotes Brazil 73.77 99.92 99.92 99.92 100 100 100 100 100 99.92
T96 12080-12143 Sentence denotes USA 73.77 99.92 99.92 99.92 100 100 100 100 100 99.92
T97 12144-12209 Sentence denotes Wuhan 73.77 99.92 99.92 99.92 100 100 100 100 100 99.92
T98 12210-12278 Sentence denotes Pakistan 73.77 99.92 99.92 99.92 100 100 100 100 100 99.92
T99 12279-12344 Sentence denotes Italy 73.77 99.92 99.92 99.92 100 100 100 100 100 99.92
T100 12345-12422 Sentence denotes Australia 73.77 99.84 99.84 99.84 99.92 99.92 99.92 99.92 99.92 100
T101 12424-12449 Sentence denotes Molecular docking studies
T102 12450-12561 Sentence denotes The three-dimensional structure of the SARS-CoV spike protein and SARS-CoV-2 Spike protein RBD has been solved.
T103 12562-12701 Sentence denotes The PDB files of the SARS-CoV spike protein (6CRV) and the Spike protein RBD of the SARS-CoV-2 (6M0J) was downloaded from the PDB databank.
T104 12702-12847 Sentence denotes These structures were used to predict the ability of the binding of curcumin and its derivatives to the spike proteins of the two corona viruses.
T105 12848-12953 Sentence denotes Curcumin and 24 of its derivatives (Figure 1 and Supplementary Figure 2) were docked on to 6CRV and 6M0J.
T106 12954-13172 Sentence denotes Tables 2 and 3 gives the binding energies of curcumin and its derivatives with 6CRV (binding energies ranged from −10.98 to −5.12 kcal/mol) and with 6M0J (binding energies ranged −10.01 to −5.33 kcal/mol) respectively.
T107 13173-13558 Sentence denotes Visual examination of the computationally docked optimal binding poses of curcumin and its derivatives on 6CRV and 6MOJ revealed the important role of various types of interactions viz. hydrogen bonding and hydrophobic interactions, including π–π stacking, π–cation, and π–σ interactions in the stability of the binding of the curcumin/derivatives to the spike protein (6CRV and 6M0J).
T108 13559-13639 Sentence denotes All compounds showed one or more hydrogen bonds with 6CRV and 6M0J except a few.
T109 13640-13649 Sentence denotes Figure 2.
T110 13651-14110 Sentence denotes Molecular docking of Bis-demethoxy curcumin on SARS-CoV spike protein (6CRV). (A) 3 D structure of SARS-CoV Spike Glycoprotein Macromolecule (6CRV). (B) Binding Interaction of Bis-demethoxy curcumin with amino acid residues of SARS-CoV Spike glycoprotein (PDB ID-6CRV). (C) Superimposed binding mode of Bis-demethoxy curcumin with SARS-CoV Spike protein. (D) 2 D representation of the binding interaction of Bis-demethoxy curcumin with SARS-CoV Spike protein.
T111 14111-14119 Sentence denotes Table 2.
T112 14121-14214 Sentence denotes Molecular docking results of curcumin and its derivatives with SARS-CoV Spike protein (6CRV).
T113 14215-14281 Sentence denotes The top hits with the binding energy lesser than -8.4 are in bold.
T114 14282-14363 Sentence denotes Compound Binding Energy (ΔG) Ligand Efficiency Intermolecular energy XPH-Bond
T115 14364-14407 Sentence denotes Curcumin –10.1 –0.14 –8.24 –10.9724
T116 14408-14443 Sentence denotes BHBC –8.28 –0.13 –7.87 –3.42239
T117 14444-14478 Sentence denotes MNC –8.01 –0.43 –6.98 –8.01452
T118 14479-14519 Sentence denotes BDMC –10.98 –0.18 –8.94 –14.0467
T119 14520-14545 Sentence denotes 1 –5.12 –0.25 –4.17 0
T120 14546-14582 Sentence denotes 2 –8.55 –0.41 –6.56 –18.4317
T121 14583-14615 Sentence denotes 3 –6.56 –0.21 –4.92 –11.1148
T122 14616-14652 Sentence denotes 4 –8.69 –0.13 –6.94 –19.1539
T123 14653-14685 Sentence denotes 5 –7.03 –0.19 –5.93 –8.47153
T124 14686-14718 Sentence denotes 6 –6.59 –0.36 –5.12 –7.41531
T125 14719-14751 Sentence denotes 7 –7.96 –0.21 –6.14 –7.98548
T126 14752-14784 Sentence denotes 8 –7.55 –0.19 –5.14 –6.14537
T127 14785-14810 Sentence denotes 9 –6.91 –0.21 –5.18 0
T128 14811-14844 Sentence denotes 10 –7.75 –0.21 –6.14 –6.73473
T129 14845-14878 Sentence denotes 11 –8.02 –0.19 –6.19 –17.2465
T130 14879-14912 Sentence denotes 12 –7.85 –0.38 –6.25 –14.6321
T131 14913-14946 Sentence denotes 13 –5.94 –0.29 –4.12 –11.3576
T132 14947-14984 Sentence denotes 14 –8.75 –0.25 –7.19 –21.1412
T133 14985-15019 Sentence denotes 15 –7.87 –0.38 –7.26 –0.473228
T134 15020-15058 Sentence denotes 16 –8.47 –0.25 –6.88 –8.458912
T135 15059-15094 Sentence denotes DMC –7.89 –0.21 –6.41 –10.47057
T136 15095-15129 Sentence denotes FAC –7.17 –0.36 –5.15 –9.14873
T137 15130-15164 Sentence denotes IBC –7.91 –0.23 –7.17 –6.90341
T138 15165-15199 Sentence denotes IVC –7.43 –0.44 –6.67 –19.9864
T139 15200-15234 Sentence denotes SYC –6.82 –0.26 –5.45 –9.44678
T140 15235-15255 Sentence denotes Abbreviations: BHBC:
T141 15256-15310 Sentence denotes 3-5-di-tert-butyl-4-hydroxybenzaldehyde curcumin, MNC:
T142 15311-15353 Sentence denotes 4-methoxy-1-naphthaldehyde curcumin, BDMC:
T143 15354-15382 Sentence denotes Bis-demethoxy curcumin, DMC:
T144 15383-15407 Sentence denotes Demethoxy curcumin, FAC:
T145 15408-15435 Sentence denotes Ferulic-acid curcumin, IBC:
T146 15436-15460 Sentence denotes Ibuprofen curcumin, IVC:
T147 15461-15487 Sentence denotes Isovanillin curcumin, SYC:
T148 15488-15512 Sentence denotes Syringaldehyde curcumin.
T149 15513-15521 Sentence denotes Table 3.
T150 15523-15643 Sentence denotes Molecular docking analysis of curcumin and its derivatives with SARS-CoV-2 Spike protein Receptor binding domain (6M0J).
T151 15644-15710 Sentence denotes The top hits with the binding energy lesser than -8.4 are in bold.
T152 15711-15792 Sentence denotes Compound Binding Energy (ΔG) Ligand Efficiency Intermolecular energy XPH-Bond
T153 15793-15836 Sentence denotes Curcumin –9.81 –0.15 –8.35 –15.1512
T154 15837-15865 Sentence denotes BHBC −5.33 –0.13 –7.96 0
T155 15866-15900 Sentence denotes MNC –7.96 –0.27 –7.38 –4.24687
T156 15901-15941 Sentence denotes BDMC –10.01 –0.12 –9.18 –13.9824
T157 15942-15974 Sentence denotes 1 –7.58 –0.36 –6.19 –18.3489
T158 15975-16009 Sentence denotes 2 –8.81 –0.31 –8.38 1.2654
T159 16010-16042 Sentence denotes 3 –6.14 –0.34 –5.45 –6.95102
T160 16043-16079 Sentence denotes 4 –8.88 –0.18 –7.98 –14.0321
T161 16080-16111 Sentence denotes 5 –6.23 –0.26 –5.88 –3.5891
T162 16112-16144 Sentence denotes 6 –7.16 –0.37 –6.15 –10.1688
T163 16145-16177 Sentence denotes 7 –6.89 –0.25 –5.98 –9.12515
T164 16178-16210 Sentence denotes 8 –5.49 –0.12 –3.90 –5.92265
T165 16211-16243 Sentence denotes 9 –6.92 –0.18 –6.22 –6.96719
T166 16244-16273 Sentence denotes 10 –7.03 –0.24 –6.33 –7.0
T167 16274-16307 Sentence denotes 11 –6.88 –0.27 –6.23 –6.44363
T168 16308-16340 Sentence denotes 12 –7.95 –0.41 –5.70 –2.5581
T169 16341-16374 Sentence denotes 13 –6.11 –0.39 –5.42 –7.34943
T170 16375-16408 Sentence denotes 14 –7.45 –0.19 –6.40 –10.5367
T171 16409-16442 Sentence denotes 15 –5.74 –0.39 –5.51 –2.36748
T172 16443-16476 Sentence denotes 16 –7.83 –0.27 –7.48 –6.64321
T173 16477-16511 Sentence denotes DMC –5.98 –0.19 –5.38 –5.99913
T174 16512-16546 Sentence denotes FAC –5.85 –0.38 –5.25 –6.46613
T175 16547-16581 Sentence denotes IBC –6.65 –0.15 –6.20 –1.52841
T176 16582-16620 Sentence denotes IVC –8.96 –0.43 –7.73 –12.2707
T177 16621-16654 Sentence denotes SYC –5.87 –0.29 –5.43 –4.4411
T178 16655-16675 Sentence denotes Abbreviations: BHBC:
T179 16676-16730 Sentence denotes 3-5-di-tert-butyl-4-hydroxybenzaldehyde curcumin, MNC:
T180 16731-16773 Sentence denotes 4-methoxy-1-naphthaldehyde curcumin, BDMC:
T181 16774-16802 Sentence denotes Bis-demethoxy curcumin, DMC:
T182 16803-16827 Sentence denotes Demethoxy curcumin, FAC:
T183 16828-16855 Sentence denotes Ferulic-acid curcumin, IBC:
T184 16856-16880 Sentence denotes Ibuprofen curcumin, IVC:
T185 16881-16907 Sentence denotes Isovanillin curcumin, SYC:
T186 16908-16932 Sentence denotes Syringaldehyde curcumin.
T187 16933-17222 Sentence denotes In 6CRV, it was found that ARG99, GLY100, TRP 101, ILE116, ILE117, ASN118, VAL123, MET144, SER165, ASP166, PHE168, ARG183, PHE185, LYS198, ILE219, PHE220 were the major amino acids involved in hydrogen bonding, hydrophobic and van der Waals interaction with most of the curcumin compounds.
T188 17223-17345 Sentence denotes However, majority of the curcumin compounds exhibited hydrogen bonding with ARG99, MET144, LYS198 except compound 1 and 9.
T189 17346-17589 Sentence denotes In addition, all the compounds exhibited hydrophobic (π–π stacking, π–cation, and π–σ) interactions with ASP166, VAL123, PHE185 and van der Waals interaction with GLY100, TRP 101, ILE117, ASN118, ARG183, ILE116, PHE168, SER165, PHE220, ILE219.
T190 17590-17749 Sentence denotes All compounds showed one or more hydrogen bonding interactions with spike RBD of the SARS-CoV-2 (6M0J) except 3-5-di-tert-butyl-4-hydroxybenzaldehyde curcumin.
T191 17750-18000 Sentence denotes It was found that ARG355, TYR396, PRO426, ASP428, THR430, GLY431, PHE429, PHE 464, GLU516, SER514, LEU517 and PHE515 were the major amino acids involved in hydrogen bonding hydrophobic and van der Waals interaction with the all of curcumin compounds.
T192 18001-18101 Sentence denotes However, majority of the curcumin compounds exhibit hydrogen bonding with ARG355, LEU517 and THR430.
T193 18102-18295 Sentence denotes In addition, the compounds exhibited hydrophobic (π–π stacking, π–cation, and π–σ) and van der Waals interactions with PHE464, GLY431, GLU516, SER514, PHE515, TYR396, PRO426, ASP428 and PHE429.
T194 18296-18446 Sentence denotes The curcumin derivative with the best binding affinity was Bis-demethoxycurcumin for both 6CRV (ΔG = −10.98 kcal/mol) and 6M0J (ΔG = −10.01 kcal/mol).
T195 18447-18563 Sentence denotes The native compound, curcumin, demonstrated a binding energy of −9.81 kcal/mol for 6M0J and −10.1 kcal/mol for 6CRV.
T196 18564-18704 Sentence denotes Binding mode of Bis-demethoxycurcumin with SARS-CoV Spike protein and SARS-CoV-2 Spike protein RBD is shown in Figure 2 and 3, respectively.
T197 18705-18714 Sentence denotes Figure 3.
T198 18716-19232 Sentence denotes Molecular docking of Bis-demethoxy curcumin on SARS-CoV-2 spike protein receptor binding domain (6M0J). (A) 3D structure of SARS-CoV-2 spike protein RBD bound with ACE2 protein Macromolecule. (B) Binding Interaction of Bis-demethoxy curcumin with amino acid residue of spike protein RBD of SARS-CoV-2 (PDB ID-6M0J). (C) Superimposed binding mode of Bis-demethoxy curcumin, docked with SARS-CoV-2 spike protein RBD. (D) 2D representation of the binding interaction of Bis-demethoxy curcumin with SARS-CoV-2 spike RBD.
T199 19234-19297 Sentence denotes In-silico drug-likeness and pharmacokinetic property prediction
T200 19298-19435 Sentence denotes All the structures used for docking were analysed for in silico drug-likeness based on the Lipinski’s rules using pkCSM server (Table 4).
T201 19436-19592 Sentence denotes The lipophilicity (expressed as LogP) predicted for all the compounds were found to be well above the traditionally cut-off value of 5 used for drug design.
T202 19593-19746 Sentence denotes Curcumin and its derivatives, used in this study, show suitable MW values (MW < 500) essential for a successful penetration through biological membranes.
T203 19747-19873 Sentence denotes The surface area (SA) for all the compounds was observed to be in the range 115.89 − 240.65 Å2 which is well within the limit.
T204 19874-20131 Sentence denotes All compounds, except 5-di-tert-butyl-4-hydroxybenzaldehyde curcumin (BHBC), 4-methoxy-1-naphthaldehyde curcumin (MNC), Syringaldehyde curcumin (SYC) and compound-16, fall into the appropriate range indicating good bioavailability of the candidate molecule.
T205 20132-20276 Sentence denotes The number of hydrogen bond acceptors (HBA, ≤10) and donors (HBD, ≤5) for all the compounds were in accordance with the Lipinski’s rule of five.
T206 20277-20285 Sentence denotes Table 4.
T207 20287-20353 Sentence denotes In-silico prediction of drug-likeness for curcumin derivatives[a].
T208 20354-20416 Sentence denotes Compound MW LogP SA HBA HBD nviolations Rotatable bonds
T209 20417-20454 Sentence denotes BHBC 534.78 8.93 236.0 4 3 1 6
T210 20455-20493 Sentence denotes MNC 538.59 6.14 232.11 7 2 1 11
T211 20494-20532 Sentence denotes BDMC 308.33 3.83 133.51 4 3   5
T212 20533-20569 Sentence denotes 1 270.353 4.21 115.89 3 1   4
T213 20570-20606 Sentence denotes 2 332.739 3.79 136.57 5 4   4
T214 20607-20643 Sentence denotes 3 314.337 3.77 133.64 5 4   4
T215 20644-20679 Sentence denotes 4 322.36 4.36 139.56 3 3   4
T216 20680-20716 Sentence denotes 5 364.441 4.93 159.62 4 0   5
T217 20717-20753 Sentence denotes 6 320.388 4.95 141.45 4 3   1
T218 20754-20789 Sentence denotes 7 325.32 3.60 138.02 5 1   6
T219 20790-20826 Sentence denotes 8 329.193 4.45 125.75 2 1   4
T220 20827-20863 Sentence denotes 9 462.181 5.24 164.71 7 2   0
T221 20864-20901 Sentence denotes 10 351.358 4.13 149.74 4 5   1
T222 20902-20939 Sentence denotes 11 360.375 5.07 149.89 2 1   3
T223 20940-20977 Sentence denotes 12 419.565 6.24 185.40 9 4   1
T224 20978-21015 Sentence denotes 13 389.495 5.22 171.67 4 4   1
T225 21016-21053 Sentence denotes 14 342.778 3.81 143.82 4 2   2
T226 21054-21091 Sentence denotes 15 469.629 4.38 208.20 6 5   1
T227 21092-21130 Sentence denotes 16 486.564 6.19 211.58 11 6 1 0
T228 21131-21169 Sentence denotes DMC 342.391 3.20 146.43 5 2   9
T229 21170-21208 Sentence denotes FAC 550.604 4.7 232.81 9 2   15
T230 21209-21248 Sentence denotes IBC 556.655 5.24 240.62 7 1   15
T231 21249-21288 Sentence denotes IVC 504.535 4.69 214.22 8 3   11
T232 21289-21328 Sentence denotes SYC 430.453 3.77 180.12 10 8 1 3
T233 21329-21544 Sentence denotes [a]  MW = Molecular weight, LogP = octanol-water partition coefficient, SA = Surface Area, HBA = Number of hydrogen bond acceptor, HBD = Number of hydrogen bond donor, nviolations = violations from Lipinski’s rule.
T234 21545-21550 Sentence denotes BHBC:
T235 21551-21605 Sentence denotes 3-5-di-tert-butyl-4-hydroxybenzaldehyde curcumin, MNC:
T236 21606-21648 Sentence denotes 4-methoxy-1-naphthaldehyde curcumin, BDMC:
T237 21649-21677 Sentence denotes Bis-demethoxy curcumin, DMC:
T238 21678-21702 Sentence denotes Demethoxy curcumin, FAC:
T239 21703-21730 Sentence denotes Ferulic-acid curcumin, IBC:
T240 21731-21755 Sentence denotes Ibuprofen curcumin, IVC:
T241 21756-21782 Sentence denotes Isovanillin curcumin, SYC:
T242 21783-21807 Sentence denotes Syringaldehyde curcumin.
T243 21808-21963 Sentence denotes Additionally, a variety of key ADMET (Absorption, Distribution, Metabolism and Excretion) properties have also been calculated with the aid of pkCSMserver.
T244 21964-21998 Sentence denotes The results are listed in Table 5.
T245 21999-22301 Sentence denotes All curcumin derivatives showed moderate to high water solubility ranging from −2.91 log mol/L (BHBC) to −6.99 log mol/L (compound-12), in addition to high Caco-2 permeability (permeation > 0.90) except compound BHBC and MNC (permeation = 0.67 and 0.43 respectively) which showed moderate permeability.
T246 22302-22425 Sentence denotes Intestinal absorption (IA) has been found to be greater than 85% indicating good permeation across the intestinal membrane.
T247 22426-22514 Sentence denotes Further, all curcumin compounds showed good permeation through skin (permeation > −2.5).
T248 22515-22749 Sentence denotes Additionally, all curcumin compounds showed no inhibition towards P-glycoprotein I and P-glycoprotein II, except compounds BHBC, MNC, compound-13 and Ferrulic acid curcumin (FAC) which demonstrated inhibition towards P-glycoprotein I.
T249 22750-22887 Sentence denotes Furthermore, all curcumin compounds showed poor BBB permeability and moderate CNS permeability except Isovanillin curcumin (IVC) and SYC.
T250 22888-23061 Sentence denotes All showed inhibition towards the metabolizing enzyme CYP3A4 except BHBC, compounds-8, -11, -14, -15 and -16, while except compound-15, all showed inhibition towards CYP2C9.
T251 23062-23214 Sentence denotes All curcumin derivatives were found to show the total clearance in the range 0.10 log mL/min/kg (compound-1 and -4) to 1.01 log mL/min/kg (compound-15).
T252 23215-23423 Sentence denotes Further, all curcumin derivatives except compound 15 were found to act as OCT2 substrate, thus indicating that these compounds will not have any adverse interactions and no negative effect on renal clearance.
T253 23424-23432 Sentence denotes Table 5.
T254 23434-23488 Sentence denotes In-silico ADME prediction for curcumin derivatives[a].
T255 23489-23542 Sentence denotes Comp Absorption Distribution Metabolism Excretion
T256 23543-23610 Sentence denotes   WS CP IA SP PI-1 PI-2 VD FU BBB CNS CI-1 CI-2 TC RS
T257 23611-23698 Sentence denotes BHBC –2.91 0.67 88.62 –2.73 Yes Yes –0.39 0.31 –0.67 –0.85 No Yes 0.15 No
T258 23699-23784 Sentence denotes MNC –3.64 0.43 100 –2.73 Yes Yes –1.45 0.33 –0.39 –2.73 Yes Yes 0.26 No
T259 23785-23871 Sentence denotes BDMC –4.43 1.01 95.92 –2.99 No No –0.22 0.08 –0.72 –2.11 Yes Yes 0.12 No
T260 23872-23953 Sentence denotes 1 –4.66 1.25 91.80 –2.51 No No 0.18 0.06 0.01 –1.45 Yes Yes 0.10 No
T261 23954-24037 Sentence denotes 2 –3.23 0.93 89.16 –2.76 No No –0.07 0.12 –1.07 –2.29 Yes Yes 0.05 No
T262 24038-24121 Sentence denotes 3 –3.19 0.94 89.70 –2.76 No No –0.02 0.13 –1.06 –2.27 Yes Yes 0.06 No
T263 24122-24201 Sentence denotes 4 –4.11 0.92 87.64 –3.07 No No 0.09 0 –0.74 –1.85 Yes Yes 0.10 No
T264 24202-24281 Sentence denotes 5 –6.39 1.06 94.85 –2.49 No No 0.25 0 –0.03 –1.30 Yes Yes 0.22 No
T265 24282-24361 Sentence denotes 6 –5.42 1.43 90.49 –2.73 No No 0.05 0 –0.33 –1.29 Yes Yes 0.23 No
T266 24362-24441 Sentence denotes 7 –4.54 1.04 91.97 –2.73 No No –0.37 0 0.28 –2.20 Yes Yes 0.13 No
T267 24442-24519 Sentence denotes 8 –5.09 1.66 90.44 –2.29 No No 0.27 0 0.16 –1.47 No Yes 0.14 No
T268 24520-24598 Sentence denotes 9 –7.03 1.13 93.34 –2.51 No No 0.37 0 0.46 –1.26 Yes Yes 0.26 No
T269 24599-24680 Sentence denotes 10 –4.89 0.94 91.50 –2.74 No No –0.04 0 –0.24 –1.93 Yes Yes 0.11 No
T270 24681-24759 Sentence denotes 11 –5.93 1.28 89.16 –2.59 No No 0.36 0 0.66 –1.40 No Yes 0.13 No
T271 24760-24840 Sentence denotes 12 –6.99 1.02 91.30 –2.75 No No 0.66 0 –0.32 –1.85 Yes Yes 1.04 No
T272 24841-24923 Sentence denotes 13 –5.42 1.27 92.76 –2.80 Yes Yes 0.54 0 –0.02 –1.58 Yes Yes 0.26 No
T273 24924-25007 Sentence denotes 14 –4.20 1.12 90.31 –2.92 No No –0.04 0.01 –0.31 –1.33 No Yes 0.08 No
T274 25008-25090 Sentence denotes 15 –3.76 0.97 88.86 –2.79 No No 1.90 0.16 –0.20 –1.26 No No 1.01 Yes
T275 25091-25174 Sentence denotes 16 –6.92 0.90 94.67 –2.73 No No –0.59 0.07 –0.72 –2.62 No Yes 0.41 No
T276 25175-25260 Sentence denotes DMC –3.95 0.99 92.03 –2.74 No No –0.06 0.12 –0.23 –2.66 Yes Yes 0.32 No
T277 25261-25348 Sentence denotes FAC –4.02 1.41 83.68 –2.76 Yes Yes –0.58 0.24 –0.91 –3.26 Yes Yes 0.55 No
T278 25349-25434 Sentence denotes IBC –4.36 0.91 91.72 –2.73 No No –0.88 0.18 –0.53 –2.77 Yes Yes 0.62 No
T279 25435-25520 Sentence denotes IVC –3.95 0.96 89.31 –2.73 No No –0.60 0.24 –1.37 –3.02 Yes Yes 0.16 No
T280 25521-25605 Sentence denotes SYC –3.89 1.01 89.15 –2.73 No No 0.28 0.17 –1.47 –3.14 Yes Yes 0.23 No
T281 25606-26123 Sentence denotes [a]  Abbreviations: WS—Water solubility (log mol/L), CP—Caco2 permeability (log Papp in 10-6 cm/s), IA—Human intestinal absorption (% Absorbed), SP—Skin permeability (log Kp),PI-1—P-glycoprotein I inhibitor, PI-2—P-glycoprotein II inhibitor, VD—Human volume ofdistribution (log L/kg), FU—Fraction unbound (human) (Fu), BBB—BBB permeability (logBB), CNS—CNS permeability (log PS), CI-1—CYP3A4 inhibitor, CI-2—CYP2C9 inhibitor,TC—Total clearance (log mL/min/kg), RS—Renal OCT2 (organic cation transporter 2) substrate.
T282 26124-26129 Sentence denotes BHBC:
T283 26130-26184 Sentence denotes 3-5-di-tert-butyl-4-hydroxybenzaldehyde curcumin, MNC:
T284 26185-26227 Sentence denotes 4-methoxy-1-naphthaldehyde curcumin, BDMC:
T285 26228-26256 Sentence denotes Bis-demethoxy curcumin, DMC:
T286 26257-26281 Sentence denotes Demethoxy curcumin, FAC:
T287 26282-26309 Sentence denotes Ferulic-acid curcumin, IBC:
T288 26310-26334 Sentence denotes Ibuprofen curcumin, IVC:
T289 26335-26361 Sentence denotes Isovanillin curcumin, SYC:
T290 26362-26386 Sentence denotes Syringaldehyde curcumin.
T291 26388-26413 Sentence denotes Conclusion and discussion
T292 26414-26510 Sentence denotes The spike proteins of corona viruses are essential for entry of the virus into the target cells.
T293 26511-26679 Sentence denotes The spike protein exists as a trimer on the surface of the virus with one of the monomer in up conformation and the other two in down conformation (Wrapp et al., 2020).
T294 26680-26821 Sentence denotes The N-terminal region (S1) of the S protein is important for binding to the cellular receptor ACE2 (Hoffmann et al., 2020; Tai et al., 2020).
T295 26822-26998 Sentence denotes The S protein undergoes priming by cellular protease, TMPRSS2 and the S2 region of the protein is responsible for fusion of viral and cellular membrane (Hoffmann et al., 2020).
T296 26999-27158 Sentence denotes Therefore, identifying therapeutics for the S protein of the novel corona virus could potentially target the critical process of entry and fusion of the virus.
T297 27159-27274 Sentence denotes Curcumin and its derivatives are known for their many biological activities, one of them is its antiviral activity.
T298 27275-27405 Sentence denotes Therefore, here, we examined the potential of curcumin, and its derivatives, to bind to the SARS-CoV and SARS-CoV-2 spike protein.
T299 27406-27755 Sentence denotes From our computational molecular docking approach (using auto dock 4.2, PDB ID - 6CRV, 6M0J) and in-silico ADMET tool, we predicted that Bis-demethoxy curcumin, compound-4 and compound-2 were the most recommended curcumin compounds which bind to RBD domain of the SARS-CoV-2 Spike protein and SARS-CoV spike protein efficiently in in silico studies.
T300 27756-27985 Sentence denotes Curcumin has earlier shown to have specific inhibitory effect on the NA activity in influenza virus (Chen et al., 2013; Richart et al., 2018) and modulating immune response to prevent injury to the lung tissue (Han et al., 2018).
T301 27986-28134 Sentence denotes Till date, Bis-demethoxy curcumin has shown to have anti-cancer and hepato-protective activities (Kumaravel et al., 2013; Rajagopalan et al., 2010).
T302 28135-28215 Sentence denotes This is the first time; it is predicted to have a potential anti-viral activity.
T303 28216-28418 Sentence denotes Therefore, these curcumin derivatives, which have been predicted to bind to the SARS-CoV-2 spike protein, could be explored as probable inhibitors of COVID-19 spike protein through experimental studies.
T304 28420-28442 Sentence denotes Supplementary Material
T305 28443-28467 Sentence denotes Supplementary_Figure.pdf
T306 28468-28504 Sentence denotes Click here for additional data file.
T307 28506-28522 Sentence denotes Acknowledgements
T308 28523-28788 Sentence denotes We acknowledge the support rendered by the Department of Biochemistry, Indian Academy Degree College - Autonomous, Bengaluru and Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Gujarat for their support in carrying out this work.
T309 28790-28810 Sentence denotes Disclosure statement
T310 28811-28870 Sentence denotes The authors declare that they have no conflict of interests

LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
2 88-98 Species denotes SARS-CoV-2 Tax:2697049
3 21-29 Chemical denotes curcumin MESH:D003474
23 519-550 Gene denotes angiotensin converting enzyme 2 Gene:59272
24 552-556 Gene denotes ACE2 Gene:59272
25 1139-1144 Gene denotes spike Gene:43740568
26 1600-1605 Gene denotes spike Gene:43740568
27 752-757 Gene denotes Spike Gene:43740568
28 229-239 Species denotes SARS-CoV-2 Tax:2697049
29 291-309 Species denotes novel corona virus Tax:2697049
30 310-320 Species denotes SARS-CoV-2 Tax:2697049
31 334-342 Species denotes SARS-CoV Tax:694009
32 698-706 Species denotes SARS-CoV Tax:694009
33 741-751 Species denotes SARS-CoV-2 Tax:2697049
34 912-925 Species denotes Curcuma longa Tax:136217
35 1589-1599 Species denotes SARS-CoV-2 Tax:2697049
36 863-871 Chemical denotes Curcumin MESH:D003474
37 1000-1008 Chemical denotes curcumin MESH:D003474
38 1183-1191 Chemical denotes curcumin MESH:D003474
39 1363-1384 Chemical denotes bis-demethoxycurcumin MESH:C034786
40 1550-1558 Chemical denotes curcumin MESH:D003474
41 194-202 Disease denotes COVID-19 MESH:C000657245
64 1787-1800 Species denotes Coronaviruses Tax:11118
65 1884-1897 Species denotes coronaviridae Tax:11118
66 2327-2345 Species denotes novel corona virus Tax:2697049
67 2354-2364 Species denotes SARS-CoV-2 Tax:2697049
68 2400-2408 Species denotes patients Tax:9606
69 3276-3286 Species denotes SARS-CoV-2 Tax:2697049
70 1952-1972 Disease denotes respiratory diseases MESH:D012140
71 2077-2110 Disease denotes Severe Acute Respiratory Syndrome MESH:D045169
72 2122-2154 Disease denotes Middle East Respiratory Syndrome MESH:D018352
73 2156-2160 Disease denotes MERS MESH:D018352
74 2275-2284 Disease denotes pneumonia MESH:D011014
75 2390-2399 Disease denotes pneumonia MESH:D011014
76 2456-2480 Disease denotes Coronavirus disease 2019 MESH:C000657245
77 2482-2490 Disease denotes COVID-19 MESH:C000657245
78 2650-2658 Disease denotes zoonotic MESH:D015047
79 2895-2905 Disease denotes infections MESH:D007239
80 2912-2931 Disease denotes respiratory disease MESH:D012140
81 2940-2949 Disease denotes pneumonia MESH:D011014
82 2955-2974 Disease denotes respiratory failure MESH:D012131
83 2984-2989 Disease denotes death MESH:D003643
84 3054-3062 Disease denotes COVID-19 MESH:C000657245
85 3238-3247 Disease denotes infection MESH:D007239
104 3503-3508 Gene denotes spike Gene:43740568
105 3544-3560 Gene denotes envelope protein Gene:64006
106 3615-3620 Gene denotes Spike Gene:43740568
107 4000-4005 Gene denotes spike Gene:43740568
108 4073-4077 Gene denotes ACE2 Gene:59272
109 4148-4155 Gene denotes TMPRSS2 Gene:7113
110 4227-4234 Gene denotes TMPRSS2 Gene:7113
111 4326-4331 Gene denotes spike Gene:43740568
112 3294-3304 Species denotes SARS-CoV-2 Tax:2697049
113 3637-3655 Species denotes beta coronaviruses Tax:694002
114 3656-3666 Species denotes SARS-CoV-2 Tax:2697049
115 3671-3679 Species denotes SARS-CoV Tax:694009
116 3764-3770 Species denotes humans Tax:9606
117 4022-4039 Species denotes novel coronavirus Tax:2697049
118 4054-4062 Species denotes SARS-CoV Tax:694009
119 4262-4279 Species denotes novel coronavirus Tax:2697049
120 4347-4364 Species denotes novel coronavirus Tax:2697049
121 4183-4189 Chemical denotes serine MESH:D012694
134 5529-5534 Gene denotes spike Gene:43740568
135 4598-4611 Species denotes Curcuma longa Tax:136217
136 5395-5410 Species denotes influenza virus Tax:11308
137 5550-5558 Species denotes SARS-CoV Tax:694009
138 5567-5577 Species denotes SARS-CoV-2 Tax:2697049
139 4525-4533 Chemical denotes Curcumin MESH:D003474
140 4824-4832 Chemical denotes Curcumin MESH:D003474
141 5147-5155 Chemical denotes curcumin MESH:D003474
142 5317-5325 Chemical denotes Curcumin MESH:D003474
143 5479-5487 Chemical denotes curcumin MESH:D003474
144 4707-4713 Disease denotes cancer MESH:D009369
145 5191-5206 Disease denotes virus infection MESH:D001102
155 5819-5824 Gene denotes spike Gene:43740568
156 5706-5711 Gene denotes spike Gene:43740568
157 5845-5853 Species denotes SARS-CoV Tax:694009
158 5862-5880 Species denotes novel corona virus Tax:2697049
159 5882-5892 Species denotes SARS-CoV-2 Tax:2697049
160 5629-5637 Chemical denotes curcumin MESH:D003474
161 5756-5777 Chemical denotes bis-demethoxycurcumin MESH:C034786
162 5925-5933 Chemical denotes curcumin MESH:D003474
163 6034-6042 Disease denotes COVID-19 MESH:C000657245
166 6106-6116 Species denotes SARS-CoV-2 Tax:2697049
167 6121-6129 Species denotes SARS-CoV Tax:694009
177 6566-6570 Gene denotes ACE2 Gene:59272
178 6650-6654 Gene denotes Bank Gene:55024
179 6460-6468 Species denotes SARS-CoV Tax:694009
180 6540-6550 Species denotes SARS-CoV-2 Tax:2697049
181 6560-6565 Species denotes human Tax:9606
182 6849-6854 Chemical denotes water MESH:D014867
183 6913-6921 Chemical denotes hydrogen MESH:D006859
184 7001-7010 Chemical denotes hydrogens MESH:D006859
185 6941-6958 Disease denotes Gasteiger-Marsili
187 7165-7173 Chemical denotes curcumin MESH:D003474
189 7580-7588 Chemical denotes curcumin MESH:D003474
194 8104-8109 Gene denotes spike Gene:43740568
195 8298-8324 Gene denotes spike surface glycoprotein
196 8121-8129 Species denotes SARS-CoV Tax:694009
197 8155-8165 Species denotes SARS-CoV-2 Tax:2697049
199 9038-9045 Disease denotes elitism
210 10277-10283 Gene denotes CYP3A4 Gene:1576
211 10288-10294 Gene denotes CYP2C9 Gene:1559
212 10352-10356 Gene denotes OCT2 Gene:6582
213 10358-10386 Gene denotes organic cation transporter 2 Gene:6582
214 10084-10089 Species denotes human Tax:9606
215 9893-9900 Chemical denotes octanol MESH:D000442
216 9901-9906 Chemical denotes water MESH:D014867
217 10021-10029 Chemical denotes curcumin MESH:D003474
218 10046-10051 Chemical denotes water MESH:D014867
219 10064-10069 Chemical denotes Caco2
223 10473-10478 Gene denotes spike Gene:43740568
224 10449-10459 Species denotes SARS-CoV-2 Tax:2697049
225 10464-10472 Species denotes SARS-CoV Tax:694009
239 10973-10978 Gene denotes spike Gene:43740568
240 10908-10913 Gene denotes spike Gene:43740568
241 10800-10805 Gene denotes spike Gene:43740568
242 10593-10598 Gene denotes spike Gene:43740568
243 10615-10633 Species denotes novel corona virus Tax:2697049
244 10635-10645 Species denotes SARS-CoV-2 Tax:2697049
245 10659-10667 Species denotes SARS-CoV Tax:694009
246 10821-10839 Species denotes novel corona virus Tax:2697049
247 10840-10850 Species denotes SARS-CoV-2 Tax:2697049
248 10897-10907 Species denotes SARS-CoV-2 Tax:2697049
249 10937-10945 Species denotes SARS-CoV Tax:694009
250 10962-10972 Species denotes SARS-CoV-2 Tax:2697049
251 11010-11018 Species denotes SARS-CoV Tax:694009
256 11210-11215 Gene denotes spike Gene:43740568
257 11186-11196 Species denotes SARS-CoV-2 Tax:2697049
258 11201-11209 Species denotes SARS-CoV Tax:694009
259 11115-11123 Chemical denotes curcumin MESH:D003474
268 11266-11271 Gene denotes Spike Gene:43740568
269 11506-11511 Gene denotes spike Gene:43740568
270 11555-11560 Gene denotes spike Gene:43740568
271 11592-11597 Gene denotes spike Gene:43740568
272 11288-11298 Species denotes SARS-CoV-2 Tax:2697049
273 11303-11311 Species denotes SARS-CoV Tax:694009
274 11526-11536 Species denotes SARS-CoV-2 Tax:2697049
275 11583-11591 Species denotes SARS-CoV Tax:694009
278 11628-11636 Species denotes SARS-CoV Tax:694009
279 11710-11718 Species denotes SARS-CoV Tax:694009
297 12527-12532 Gene denotes Spike Gene:43740568
298 12621-12626 Gene denotes Spike Gene:43740568
299 13528-13533 Gene denotes spike Gene:43740568
300 12498-12503 Gene denotes spike Gene:43740568
301 12806-12811 Gene denotes spike Gene:43740568
302 12592-12597 Gene denotes spike Gene:43740568
303 12489-12497 Species denotes SARS-CoV Tax:694009
304 12516-12526 Species denotes SARS-CoV-2 Tax:2697049
305 12583-12591 Species denotes SARS-CoV Tax:694009
306 12646-12656 Species denotes SARS-CoV-2 Tax:2697049
307 12770-12778 Chemical denotes curcumin MESH:D003474
308 12848-12856 Chemical denotes Curcumin MESH:D003474
309 12999-13007 Chemical denotes curcumin MESH:D003474
310 13247-13255 Chemical denotes curcumin MESH:D003474
311 13359-13367 Chemical denotes hydrogen MESH:D006859
312 13500-13508 Chemical denotes curcumin MESH:D003474
313 13592-13600 Chemical denotes hydrogen MESH:D006859
328 14096-14101 Gene denotes Spike Gene:43740568
329 13887-13892 Gene denotes Spike Gene:43740568
330 13759-13764 Gene denotes Spike Gene:43740568
331 13707-13712 Gene denotes spike Gene:43740568
332 13698-13706 Species denotes SARS-CoV Tax:694009
333 13750-13758 Species denotes SARS-CoV Tax:694009
334 13878-13886 Species denotes SARS-CoV Tax:694009
335 13982-13990 Species denotes SARS-CoV Tax:694009
336 14087-14095 Species denotes SARS-CoV Tax:694009
337 13991-13996 Gene denotes Spike Gene:43740568
338 13672-13694 Chemical denotes Bis-demethoxy curcumin MESH:C034786
339 13827-13849 Chemical denotes Bis-demethoxy curcumin MESH:C034786
340 13954-13976 Chemical denotes Bis-demethoxy curcumin MESH:C034786
341 14059-14081 Chemical denotes Bis-demethoxy curcumin MESH:C034786
345 14193-14198 Gene denotes Spike Gene:43740568
346 14184-14192 Species denotes SARS-CoV Tax:694009
347 14150-14158 Chemical denotes curcumin MESH:D003474
351 15587-15597 Species denotes SARS-CoV-2 Tax:2697049
352 15598-15603 Gene denotes Spike Gene:43740568
353 15553-15561 Chemical denotes curcumin MESH:D003474
390 16960-16965 Gene denotes ARG99 Gene:83857
391 17299-17304 Gene denotes ARG99 Gene:83857
392 16967-16973 Chemical denotes GLY100
393 16975-16978 Chemical denotes TRP MESH:D014364
394 16984-16990 Chemical denotes ILE116
395 16992-16998 Chemical denotes ILE117
396 17000-17006 Chemical denotes ASN118
397 17008-17014 Chemical denotes VAL123
398 17016-17022 Chemical denotes MET144
399 17024-17030 Chemical denotes SER165
400 17032-17038 Chemical denotes ASP166
401 17040-17046 Chemical denotes PHE168
402 17048-17054 Chemical denotes ARG183
403 17056-17062 Chemical denotes PHE185
404 17064-17070 Chemical denotes LYS198
405 17072-17078 Chemical denotes ILE219
406 17080-17086 Chemical denotes PHE220
407 17126-17134 Chemical denotes hydrogen MESH:D006859
408 17203-17211 Chemical denotes curcumin MESH:D003474
409 17248-17256 Chemical denotes curcumin MESH:D003474
410 17277-17285 Chemical denotes hydrogen MESH:D006859
411 17306-17312 Chemical denotes MET144
412 17314-17320 Chemical denotes LYS198
413 17451-17457 Chemical denotes ASP166
414 17459-17465 Chemical denotes VAL123
415 17467-17473 Chemical denotes PHE185
416 17509-17515 Chemical denotes GLY100
417 17517-17520 Chemical denotes TRP MESH:D014364
418 17526-17532 Chemical denotes ILE117
419 17534-17540 Chemical denotes ASN118
420 17542-17548 Chemical denotes ARG183
421 17550-17556 Chemical denotes ILE116
422 17558-17564 Chemical denotes PHE168
423 17566-17572 Chemical denotes SER165
424 17574-17580 Chemical denotes PHE220
425 17582-17588 Chemical denotes ILE219
457 17658-17663 Gene denotes spike Gene:43740568
458 17675-17685 Species denotes SARS-CoV-2 Tax:2697049
459 17623-17631 Chemical denotes hydrogen MESH:D006859
460 17700-17739 Chemical denotes 3-5-di-tert-butyl-4-hydroxybenzaldehyde MESH:C513957
461 17740-17748 Chemical denotes curcumin MESH:D003474
462 17768-17774 Chemical denotes ARG355
463 17776-17782 Chemical denotes TYR396
464 17784-17790 Chemical denotes PRO426
465 17792-17798 Chemical denotes ASP428
466 17800-17806 Chemical denotes THR430
467 17816-17822 Chemical denotes PHE429
468 17824-17827 Chemical denotes PHE MESH:D010649
469 17833-17839 Chemical denotes GLU516
470 17841-17847 Chemical denotes SER514
471 17849-17855 Chemical denotes LEU517
472 17860-17866 Chemical denotes PHE515
473 17906-17914 Chemical denotes hydrogen MESH:D006859
474 17981-17989 Chemical denotes curcumin MESH:D003474
475 18026-18034 Chemical denotes curcumin MESH:D003474
476 18053-18061 Chemical denotes hydrogen MESH:D006859
477 18075-18081 Chemical denotes ARG355
478 18083-18089 Chemical denotes LEU517
479 18094-18100 Chemical denotes THR430
480 18221-18227 Chemical denotes PHE464
481 18237-18243 Chemical denotes GLU516
482 18245-18251 Chemical denotes SER514
483 18253-18259 Chemical denotes PHE515
484 18261-18267 Chemical denotes TYR396
485 18269-18275 Chemical denotes PRO426
486 18277-18283 Chemical denotes ASP428
487 18288-18294 Chemical denotes PHE429
496 18616-18621 Gene denotes Spike Gene:43740568
497 18645-18650 Gene denotes Spike Gene:43740568
498 18607-18615 Species denotes SARS-CoV Tax:694009
499 18634-18644 Species denotes SARS-CoV-2 Tax:2697049
500 18300-18308 Chemical denotes curcumin MESH:D003474
501 18355-18376 Chemical denotes Bis-demethoxycurcumin MESH:C034786
502 18468-18476 Chemical denotes curcumin MESH:D003474
503 18580-18601 Chemical denotes Bis-demethoxycurcumin MESH:C034786
519 18851-18856 Gene denotes spike Gene:43740568
520 18880-18884 Gene denotes ACE2 Gene:59272
521 18985-18990 Gene denotes spike Gene:43740568
522 19112-19117 Gene denotes spike Gene:43740568
523 19222-19227 Gene denotes spike Gene:43740568
524 18763-18773 Species denotes SARS-CoV-2 Tax:2697049
525 18840-18850 Species denotes SARS-CoV-2 Tax:2697049
526 19006-19016 Species denotes SARS-CoV-2 Tax:2697049
527 19101-19111 Species denotes SARS-CoV-2 Tax:2697049
528 19211-19221 Species denotes SARS-CoV-2 Tax:2697049
529 18774-18779 Gene denotes spike Gene:43740568
530 18737-18759 Chemical denotes Bis-demethoxy curcumin MESH:C034786
531 18935-18957 Chemical denotes Bis-demethoxy curcumin MESH:C034786
532 19065-19087 Chemical denotes Bis-demethoxy curcumin MESH:C034786
533 19183-19205 Chemical denotes Bis-demethoxy curcumin MESH:C034786
543 19593-19601 Chemical denotes Curcumin MESH:D003474
544 19896-19942 Chemical denotes 5-di-tert-butyl-4-hydroxybenzaldehyde curcumin
545 19944-19948 Chemical denotes BHBC
546 19951-19977 Chemical denotes 4-methoxy-1-naphthaldehyde
547 19978-19986 Chemical denotes curcumin MESH:D003474
548 19988-19991 Chemical denotes MNC
549 19994-20017 Chemical denotes Syringaldehyde curcumin
550 20146-20154 Chemical denotes hydrogen MESH:D006859
551 20193-20196 Disease denotes HBD MESH:C564145
553 20329-20337 Chemical denotes curcumin MESH:D003474
557 20417-20421 Chemical denotes BHBC
558 20494-20498 Chemical denotes BDMC
559 20383-20386 Disease denotes HBD MESH:C564145
581 21365-21372 Chemical denotes octanol MESH:D000442
582 21373-21378 Chemical denotes water MESH:D014867
583 21437-21445 Chemical denotes hydrogen MESH:D006859
584 21477-21485 Chemical denotes hydrogen MESH:D006859
585 21545-21549 Chemical denotes BHBC
586 21551-21590 Chemical denotes 3-5-di-tert-butyl-4-hydroxybenzaldehyde MESH:C513957
587 21591-21599 Chemical denotes curcumin MESH:D003474
588 21601-21604 Chemical denotes MNC
589 21606-21632 Chemical denotes 4-methoxy-1-naphthaldehyde
590 21633-21641 Chemical denotes curcumin MESH:D003474
591 21643-21647 Chemical denotes BDMC
592 21649-21671 Chemical denotes Bis-demethoxy curcumin MESH:C034786
593 21678-21696 Chemical denotes Demethoxy curcumin MESH:C050229
594 21703-21715 Chemical denotes Ferulic-acid MESH:C004999
595 21716-21724 Chemical denotes curcumin MESH:D003474
596 21726-21729 Chemical denotes IBC MESH:D002015
597 21731-21749 Chemical denotes Ibuprofen curcumin
598 21756-21776 Chemical denotes Isovanillin curcumin
599 21783-21797 Chemical denotes Syringaldehyde MESH:C069665
600 21798-21806 Chemical denotes curcumin MESH:D003474
601 21461-21464 Disease denotes HBD MESH:C564145
625 22581-22595 Gene denotes P-glycoprotein Gene:5243
626 22602-22616 Gene denotes P-glycoprotein Gene:5243
627 22942-22948 Gene denotes CYP3A4 Gene:1576
628 22962-22996 Gene denotes compounds-8, -11, -14, -15 and -16
629 23054-23060 Gene denotes CYP2C9 Gene:1559
630 23158-23176 Gene denotes (compound-1 and -4
631 23289-23293 Gene denotes OCT2 Gene:6582
632 21839-21844 Chemical denotes ADMET
633 22003-22011 Chemical denotes curcumin MESH:D003474
634 22048-22053 Chemical denotes water MESH:D014867
635 22095-22099 Chemical denotes BHBC
636 22155-22161 Chemical denotes Caco-2
637 22211-22215 Chemical denotes BHBC
638 22439-22447 Chemical denotes curcumin MESH:D003474
639 22533-22541 Chemical denotes curcumin MESH:D003474
640 22638-22642 Chemical denotes BHBC
641 22665-22687 Chemical denotes Ferrulic acid curcumin
642 22767-22775 Chemical denotes curcumin MESH:D003474
643 22852-22872 Chemical denotes Isovanillin curcumin
644 22874-22877 Chemical denotes IVC
645 22956-22960 Chemical denotes BHBC
646 23066-23074 Chemical denotes curcumin MESH:D003474
647 23228-23236 Chemical denotes curcumin MESH:D003474
649 23464-23472 Chemical denotes curcumin MESH:D003474
653 23611-23615 Chemical denotes BHBC
654 23785-23789 Chemical denotes BDMC
655 23521-23556 Disease denotes Metabolism Excretion   WS CP IA MESH:D018980
683 25787-25801 Gene denotes P-glycoprotein Gene:5243
684 25992-25998 Gene denotes CYP3A4 Gene:1576
685 26015-26021 Gene denotes CYP2C9 Gene:1559
686 26077-26081 Gene denotes OCT2 Gene:6582
687 26083-26111 Gene denotes organic cation transporter 2 Gene:6582
688 25710-25715 Species denotes Human Tax:9606
689 25815-25819 Species denotes PI-2 Tax:1214577
690 25852-25857 Species denotes Human Tax:9606
691 25913-25918 Species denotes human Tax:9606
692 25820-25834 Gene denotes P-glycoprotein Gene:5243
693 25630-25635 Chemical denotes Water MESH:D014867
694 26124-26128 Chemical denotes BHBC
695 26130-26169 Chemical denotes 3-5-di-tert-butyl-4-hydroxybenzaldehyde MESH:C513957
696 26170-26178 Chemical denotes curcumin MESH:D003474
697 26180-26183 Chemical denotes MNC
698 26185-26211 Chemical denotes 4-methoxy-1-naphthaldehyde
699 26212-26220 Chemical denotes curcumin MESH:D003474
700 26222-26226 Chemical denotes BDMC
701 26228-26250 Chemical denotes Bis-demethoxy curcumin MESH:C034786
702 26257-26275 Chemical denotes Demethoxy curcumin MESH:C050229
703 26282-26294 Chemical denotes Ferulic-acid MESH:C004999
704 26295-26303 Chemical denotes curcumin MESH:D003474
705 26305-26308 Chemical denotes IBC MESH:D002015
706 26310-26328 Chemical denotes Ibuprofen curcumin
707 26335-26355 Chemical denotes Isovanillin curcumin
708 26362-26376 Chemical denotes Syringaldehyde MESH:C069665
709 26377-26385 Chemical denotes curcumin MESH:D003474
715 26515-26520 Gene denotes spike Gene:43740568
716 26774-26778 Gene denotes ACE2 Gene:59272
717 26876-26883 Gene denotes TMPRSS2 Gene:7113
718 26418-26423 Gene denotes spike Gene:43740568
719 27060-27078 Species denotes novel corona virus Tax:2697049
731 27391-27396 Gene denotes spike Gene:43740568
732 27681-27686 Gene denotes Spike Gene:43740568
733 27708-27713 Gene denotes spike Gene:43740568
734 27367-27375 Species denotes SARS-CoV Tax:694009
735 27380-27390 Species denotes SARS-CoV-2 Tax:2697049
736 27670-27680 Species denotes SARS-CoV-2 Tax:2697049
737 27699-27707 Species denotes SARS-CoV Tax:694009
738 27159-27167 Chemical denotes Curcumin MESH:D003474
739 27321-27329 Chemical denotes curcumin MESH:D003474
740 27543-27565 Chemical denotes Bis-demethoxy curcumin MESH:C034786
741 27619-27627 Chemical denotes curcumin MESH:D003474
751 28307-28312 Gene denotes spike Gene:43740568
752 28375-28380 Gene denotes spike Gene:43740568
753 27840-27855 Species denotes influenza virus Tax:11308
754 28296-28306 Species denotes SARS-CoV-2 Tax:2697049
755 27756-27764 Chemical denotes Curcumin MESH:D003474
756 27997-28019 Chemical denotes Bis-demethoxy curcumin MESH:C034786
757 28233-28241 Chemical denotes curcumin MESH:D003474
758 28043-28049 Disease denotes cancer MESH:D009369
759 28366-28374 Disease denotes COVID-19 MESH:C000657245