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PMC:7073332 / 18032-21352 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
461 1754-1758 Species denotes HCoV Tax:694448
474 2571-2588 Gene denotes estrogen receptor Gene:2099
475 2096-2101 Species denotes human Tax:9606
476 1986-1990 Species denotes HCoV Tax:694448
477 2063-2067 Species denotes HCoV Tax:694448
478 2160-2164 Species denotes HCoV Tax:694448
479 2341-2345 Chemical denotes GSEA
480 2519-2529 Chemical denotes toremifene MESH:D017312
481 2603-2613 Chemical denotes irbesartan MESH:D000077405
482 2651-2665 Chemical denotes mercaptopurine MESH:D015122
483 2748-2757 Chemical denotes melatonin MESH:D008550
484 2770-2775 Chemical denotes amine MESH:D000588
485 2799-2821 Disease denotes rhythm sleep disorders MESH:D012893
504 3260-3272 Gene denotes HSV-1 and -2
505 2970-2991 Species denotes hepatitis delta virus Tax:12475
506 2993-2997 Species denotes EBOV Tax:1570291
507 2998-3003 Species denotes Ebola Tax:1570291
508 3013-3018 Species denotes ZEBOV Tax:186538
509 3022-3039 Species denotes Zaire Ebola virus Tax:186538
510 3092-3110 Species denotes Epstein-Barr virus Tax:10376
511 3117-3138 Species denotes Andes orthohantavirus Tax:1980456
512 3140-3144 Species denotes EMCV Tax:12104
513 3145-3171 Species denotes encephalomyocarditis virus Tax:12104
514 3173-3177 Species denotes FECV Tax:12663
515 3178-3204 Species denotes feline enteric coronavirus Tax:12663
516 3210-3237 Species denotes respiratory syncytial virus Tax:12814
517 3239-3243 Species denotes EV71 Tax:39054
518 3244-3258 Species denotes enterovirus 71 Tax:39054
519 3297-3301 Species denotes CVB4 Tax:12073
520 3302-3319 Species denotes Coxsackievirus B4 Tax:12073
521 3054-3086 Disease denotes HIV human immunodeficiency virus MESH:D015658
538 1062-1079 Gene denotes estrogen receptor Gene:2099
539 145-153 Species denotes MERS-CoV Tax:1335626
540 336-341 Species denotes human Tax:9606
541 631-635 Species denotes HCoV Tax:694448
542 788-792 Species denotes HCoV Tax:694448
543 445-449 Chemical denotes GSEA
544 807-811 Chemical denotes GSEA
545 912-922 Chemical denotes Mesalazine MESH:D019804
546 974-983 Chemical denotes sirolimus MESH:D020123
547 1026-1033 Chemical denotes equilin MESH:D004857
548 1126-1130 Chemical denotes GSEA
549 1156-1166 Chemical denotes paroxetine MESH:D017374
550 1171-1180 Chemical denotes melatonin MESH:D008550
551 1494-1498 Chemical denotes GSEA
552 158-175 Disease denotes SARS-CoV infected MESH:C000657245
553 945-971 Disease denotes inflammatory bowel disease MESH:D015212

LitCovid-PD-FMA-UBERON

Id Subject Object Predicate Lexical cue fma_id
T87 81-85 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T88 181-186 Body_part denotes cells http://purl.org/sig/ont/fma/fma68646
T89 240-244 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T90 299-303 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T91 342-346 Body_part denotes cell http://purl.org/sig/ont/fma/fma68646
T92 375-378 Body_part denotes Map http://purl.org/sig/ont/fma/fma67847
T93 412-416 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T94 742-746 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T95 958-963 Body_part denotes bowel http://purl.org/sig/ont/fma/fma7199
T96 1062-1070 Body_part denotes estrogen http://purl.org/sig/ont/fma/fma83376
T97 1171-1180 Body_part denotes melatonin http://purl.org/sig/ont/fma/fma74644
T98 1746-1753 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T99 1837-1841 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T100 2002-2010 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T101 2079-2087 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T102 2102-2109 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T103 2110-2117 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T104 2176-2183 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T105 2221-2229 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T106 2296-2304 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T107 2571-2579 Body_part denotes estrogen http://purl.org/sig/ont/fma/fma83376
T108 2748-2757 Body_part denotes melatonin http://purl.org/sig/ont/fma/fma74644
T109 2761-2775 Body_part denotes biogenic amine http://purl.org/sig/ont/fma/fma67161
T110 3040-3052 Body_part denotes glycoprotein http://purl.org/sig/ont/fma/fma62925
T111 3054-3057 Body_part denotes HIV http://purl.org/sig/ont/fma/fma278683

LitCovid-PD-MONDO

Id Subject Object Predicate Lexical cue mondo_id
T69 158-166 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T70 945-971 Disease denotes inflammatory bowel disease http://purl.obolibrary.org/obo/MONDO_0005265
T71 2789-2821 Disease denotes circadian rhythm sleep disorders http://purl.obolibrary.org/obo/MONDO_0024361
T72 2806-2821 Disease denotes sleep disorders http://purl.obolibrary.org/obo/MONDO_0003406
T73 2924-2935 Disease denotes hepatitis B http://purl.obolibrary.org/obo/MONDO_0005344
T74 2924-2933 Disease denotes hepatitis http://purl.obolibrary.org/obo/MONDO_0002251
T75 2947-2958 Disease denotes hepatitis C http://purl.obolibrary.org/obo/MONDO_0005231
T76 2947-2956 Disease denotes hepatitis http://purl.obolibrary.org/obo/MONDO_0002251
T77 2966-2969 Disease denotes HDV http://purl.obolibrary.org/obo/MONDO_0005789
T78 2970-2985 Disease denotes hepatitis delta http://purl.obolibrary.org/obo/MONDO_0005789
T79 2970-2979 Disease denotes hepatitis http://purl.obolibrary.org/obo/MONDO_0002251
T80 2998-3003 Disease denotes Ebola http://purl.obolibrary.org/obo/MONDO_0005737
T81 3028-3033 Disease denotes Ebola http://purl.obolibrary.org/obo/MONDO_0005737
T82 3064-3080 Disease denotes immunodeficiency http://purl.obolibrary.org/obo/MONDO_0021094
T83 3273-3287 Disease denotes herpes simplex http://purl.obolibrary.org/obo/MONDO_0004609

LitCovid-PD-CLO

Id Subject Object Predicate Lexical cue
T119 81-85 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T120 181-186 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T121 240-244 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T122 299-303 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T123 336-352 http://www.ebi.ac.uk/cellline#human_cell_line denotes human cell lines
T124 412-416 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T125 443-444 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T126 603-605 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T127 650-652 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T128 683-687 http://purl.obolibrary.org/obo/UBERON_0000473 denotes test
T129 713-714 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T130 742-746 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T131 766-767 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T132 777-778 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T133 895-896 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T134 1062-1079 http://purl.obolibrary.org/obo/PR_000007204 denotes estrogen receptor
T135 1335-1336 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T136 1413-1414 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T137 1728-1729 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T138 1804-1805 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T139 1837-1841 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T140 2096-2109 http://purl.obolibrary.org/obo/PR_000029067 denotes human protein
T141 2450-2451 http://purl.obolibrary.org/obo/CLO_0001021 denotes b
T142 2517-2518 http://purl.obolibrary.org/obo/CLO_0001021 denotes b
T143 2571-2588 http://purl.obolibrary.org/obo/PR_000007204 denotes estrogen receptor
T144 2759-2760 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T145 2934-2935 http://purl.obolibrary.org/obo/CLO_0001021 denotes B
T146 2936-2941 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T147 2959-2964 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T148 2986-2991 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T149 3004-3011 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes viruses
T150 3034-3039 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T151 3058-3063 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T152 3081-3086 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T153 3105-3110 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T154 3166-3171 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T155 3232-3237 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T156 3256-3258 http://purl.obolibrary.org/obo/CLO_0054055 denotes 71
T157 3288-3295 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes viruses

LitCovid-PD-CHEBI

Id Subject Object Predicate Lexical cue chebi_id
T172 41-46 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T173 323-327 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T174 407-411 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T175 479-483 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T176 561-566 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T177 603-605 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T178 650-652 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T179 768-772 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T180 906-910 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T181 912-922 Chemical denotes Mesalazine http://purl.obolibrary.org/obo/CHEBI_6775
T182 936-940 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T183 974-983 Chemical denotes sirolimus http://purl.obolibrary.org/obo/CHEBI_9168
T184 1015-1019 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T185 1026-1033 Chemical denotes equilin http://purl.obolibrary.org/obo/CHEBI_42309
T186 1047-1054 Chemical denotes agonist http://purl.obolibrary.org/obo/CHEBI_48705
T187 1062-1070 Chemical denotes estrogen http://purl.obolibrary.org/obo/CHEBI_50114
T188 1156-1166 Chemical denotes paroxetine http://purl.obolibrary.org/obo/CHEBI_7936
T189 1171-1180 Chemical denotes melatonin http://purl.obolibrary.org/obo/CHEBI_16796
T190 1253-1258 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T191 1470-1472 Chemical denotes S4 http://purl.obolibrary.org/obo/CHEBI_29401
T192 1535-1544 Chemical denotes antiviral http://purl.obolibrary.org/obo/CHEBI_22587
T193 1661-1666 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T194 1692-1701 Chemical denotes antiviral http://purl.obolibrary.org/obo/CHEBI_22587
T195 1741-1745 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T196 1746-1753 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T197 1797-1802 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T198 1910-1915 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T199 1963-1967 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T200 2002-2010 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T201 2039-2044 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T202 2079-2087 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T203 2102-2109 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T204 2110-2117 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T205 2148-2152 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T206 2176-2183 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T207 2221-2229 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T208 2296-2304 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T209 2363-2368 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T210 2389-2391 Chemical denotes NA http://purl.obolibrary.org/obo/CHEBI_33696
T211 2443-2448 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T212 2510-2515 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T213 2519-2529 Chemical denotes toremifene http://purl.obolibrary.org/obo/CHEBI_9635
T214 2571-2598 Chemical denotes estrogen receptor modulator http://purl.obolibrary.org/obo/CHEBI_50739
T215 2571-2579 Chemical denotes estrogen http://purl.obolibrary.org/obo/CHEBI_50114
T216 2580-2598 Chemical denotes receptor modulator http://purl.obolibrary.org/obo/CHEBI_90710
T217 2603-2613 Chemical denotes irbesartan http://purl.obolibrary.org/obo/CHEBI_5959
T218 2618-2629 Chemical denotes angiotensin http://purl.obolibrary.org/obo/CHEBI_48433
T219 2651-2665 Chemical denotes mercaptopurine http://purl.obolibrary.org/obo/CHEBI_50667
T220 2670-2684 Chemical denotes antimetabolite http://purl.obolibrary.org/obo/CHEBI_35221
T221 2685-2705 Chemical denotes antineoplastic agent http://purl.obolibrary.org/obo/CHEBI_35610
T222 2711-2728 Chemical denotes immunosuppressant http://purl.obolibrary.org/obo/CHEBI_35705
T223 2748-2757 Chemical denotes melatonin http://purl.obolibrary.org/obo/CHEBI_16796
T224 2770-2775 Chemical denotes amine http://purl.obolibrary.org/obo/CHEBI_32952
T225 2870-2875 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T226 2900-2909 Chemical denotes antiviral http://purl.obolibrary.org/obo/CHEBI_22587
T227 2966-2969 Chemical denotes HDV http://purl.obolibrary.org/obo/CHEBI_59113
T228 3019-3021 Chemical denotes GP http://purl.obolibrary.org/obo/CHEBI_70744
T229 3040-3052 Chemical denotes glycoprotein http://purl.obolibrary.org/obo/CHEBI_17089

LitCovid-PD-GO-BP

Id Subject Object Predicate Lexical cue
T23 299-314 http://purl.obolibrary.org/obo/GO_0010467 denotes gene expression
T24 2789-2805 http://purl.obolibrary.org/obo/GO_0007623 denotes circadian rhythm
T25 2799-2805 http://purl.obolibrary.org/obo/GO_0048511 denotes rhythm
T26 2806-2811 http://purl.obolibrary.org/obo/GO_0030431 denotes sleep

LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T2 945-971 Phenotype denotes inflammatory bowel disease http://purl.obolibrary.org/obo/HP_0002037
T3 2924-2933 Phenotype denotes hepatitis http://purl.obolibrary.org/obo/HP_0012115
T4 2947-2956 Phenotype denotes hepatitis http://purl.obolibrary.org/obo/HP_0012115
T5 2970-2979 Phenotype denotes hepatitis http://purl.obolibrary.org/obo/HP_0012115
T6 3064-3080 Phenotype denotes immunodeficiency http://purl.obolibrary.org/obo/HP_0002721

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T110 0-201 Sentence denotes To further validate the 135 repurposable drugs against HCoVs, we first performed gene set enrichment analysis (GSEA) using transcriptome data of MERS-CoV and SARS-CoV infected host cells (see Methods).
T111 202-266 Sentence denotes These transcriptome data were used as gene signatures for HCoVs.
T112 267-428 Sentence denotes Additionally, we downloaded the gene expression data of drug-treated human cell lines from the Connectivity Map (CMAP) database36 to obtain drug–gene signatures.
T113 429-567 Sentence denotes We calculated a GSEA score (see Methods) for each drug and used this score as an indication of bioinformatics validation of the 135 drugs.
T114 568-802 Sentence denotes Specifically, an enrichment score (ES) was calculated for each HCoV data set, and ES > 0 and P < 0.05 (permutation test) was used as cut-off for a significant association of gene signatures between a drug and a specific HCoV data set.
T115 803-911 Sentence denotes The GSEA score, ranging from 0 to 3, is the number of data sets that met these criteria for a specific drug.
T116 912-1203 Sentence denotes Mesalazine (an approved drug for inflammatory bowel disease), sirolimus (an approved immunosuppressive drug), and equilin (an approved agonist of the estrogen receptor for menopausal symptoms) achieved the highest GSEA scores of 3, followed by paroxetine and melatonin with GSEA scores of 2.
T117 1204-1603 Sentence denotes We next selected 16 high-confidence repurposable drugs (Fig. 5a and Table 1) against HCoVs using subject matter expertise based on a combination of factors: (i) strength of the network-predicted associations (a smaller network proximity score in Supplementary Table S4); (ii) validation by GSEA analyses; (iii) literature-reported antiviral evidence, and (iv) fewer clinically reported side effects.
T118 1604-1720 Sentence denotes Specifically, we showcased several selected repurposable drugs with literature-reported antiviral evidence as below.
T119 1721-1803 Sentence denotes Fig. 5 A discovered drug-protein-HCoV network for 16 candidate repurposable drugs.
T120 1804-1926 Sentence denotes a Network-predicted evidence and gene set enrichment analysis (GSEA) scores for 16 potential repurposable drugs for HCoVs.
T121 1927-2024 Sentence denotes The overall connectivity of the top drug candidates to the HCoV-associated proteins was examined.
T122 2025-2139 Sentence denotes Most of these drugs indirectly target HCoV-associated proteins via the human protein–protein interaction networks.
T123 2140-2271 Sentence denotes All the drug–target-HCoV-associated protein connections were examined, and those proteins with at least five connections are shown.
T124 2272-2340 Sentence denotes The box heights for the proteins indicate the number of connections.
T125 2341-2823 Sentence denotes GSEA scores for eight drugs were not available (NA) due to the lack of transcriptome profiles for the drugs. b–e Inferred mechanism-of-action networks for four selected drugs: b toremifene (first-generation nonsteroidal-selective estrogen receptor modulator), c irbesartan (an angiotensin receptor blocker), d mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties), and e melatonin (a biogenic amine for treating circadian rhythm sleep disorders).
T126 2824-2919 Sentence denotes Table 1 Top 16 network-predicted repurposable drugs with literature-derived antiviral evidence.
T127 2920-3320 Sentence denotes HBV hepatitis B virus, HCV hepatitis C virus, HDV hepatitis delta virus, EBOV Ebola viruses, ZEBOV-GP Zaire Ebola virus glycoprotein, HIV human immunodeficiency virus, EBV Epstein-Barr virus, ANDV Andes orthohantavirus, EMCV encephalomyocarditis virus, FECV feline enteric coronavirus, RSV respiratory syncytial virus, EV71 enterovirus 71, HSV-1 and -2 herpes simplex viruses, CVB4 Coxsackievirus B4.

2_test

Id Subject Object Predicate Lexical cue
32194980-17008526-19614185 394-396 17008526 denotes 36