PMC:7102591 / 26532-29991
Annnotations
LitCovid-PubTator
Id | Subject | Object | Predicate | Lexical cue | tao:has_database_id |
---|---|---|---|---|---|
829 | 227-249 | Gene | denotes | numb-associated kinase | Gene:29110 |
830 | 251-254 | Gene | denotes | NAK | Gene:29110 |
831 | 272-303 | Gene | denotes | AP2-associated protein kinase 1 | Gene:22848 |
832 | 305-309 | Gene | denotes | AAK1 | Gene:22848 |
833 | 315-341 | Gene | denotes | cyclin G-associated kinase | Gene:2580 |
834 | 343-346 | Gene | denotes | GAK | Gene:2580 |
835 | 369-373 | Gene | denotes | AAK1 | Gene:22848 |
836 | 491-495 | Gene | denotes | AAK1 | Gene:22848 |
837 | 541-545 | Gene | denotes | AAK1 | Gene:22848 |
838 | 852-855 | Gene | denotes | NAK | Gene:29110 |
839 | 1080-1084 | Gene | denotes | AAK1 | Gene:22848 |
840 | 1089-1092 | Gene | denotes | GAK | Gene:2580 |
841 | 1242-1253 | Gene | denotes | JAK 1 and 2 | Gene:3716 |
842 | 1366-1370 | Gene | denotes | IL-6 | Gene:3569 |
843 | 1787-1791 | Gene | denotes | AAK1 | Gene:22848 |
844 | 1375-1391 | Gene | denotes | interferon gamma | Gene:3458 |
845 | 64-74 | Species | denotes | SARS-CoV-2 | Tax:2697049 |
846 | 722-734 | Species | denotes | Dengue virus | Tax:12637 |
847 | 736-747 | Species | denotes | Ebola virus | Tax:205488 |
848 | 753-780 | Species | denotes | respiratory syncytial virus | Tax:12814 |
849 | 988-995 | Species | denotes | patient | Tax:9606 |
850 | 605-614 | Chemical | denotes | erlotinib | MESH:D000069347 |
851 | 616-625 | Chemical | denotes | sunitinib | MESH:D000077210 |
852 | 627-638 | Chemical | denotes | ruxolitinib | MESH:C540383 |
853 | 644-654 | Chemical | denotes | fedratinib | MESH:C528327 |
854 | 1037-1048 | Chemical | denotes | baricitinib | MESH:C000596027 |
855 | 1255-1266 | Chemical | denotes | baricitinib | MESH:C000596027 |
856 | 1520-1531 | Chemical | denotes | baricitinib | MESH:C000596027 |
857 | 1684-1703 | Chemical | denotes | lopinavir/ritonavir | MESH:C558899 |
858 | 1708-1718 | Chemical | denotes | remdesivir | MESH:C000606551 |
859 | 1741-1752 | Chemical | denotes | tofacitinib | MESH:C479163 |
860 | 1921-1933 | Chemical | denotes | upadacitinib | MESH:C000613732 |
861 | 1937-1947 | Chemical | denotes | filgotinib | MESH:C584571 |
862 | 2153-2164 | Chemical | denotes | ruxolitinib | MESH:C540383 |
863 | 700-709 | Disease | denotes | infection | MESH:D007239 |
864 | 1176-1178 | Disease | denotes | RA | MESH:D001172 |
865 | 1447-1456 | Disease | denotes | pneumonia | MESH:D011014 |
866 | 1464-1472 | Disease | denotes | COVID-19 | MESH:C000657245 |
867 | 1909-1911 | Disease | denotes | RA | MESH:D001172 |
868 | 1964-1985 | Disease | denotes | coronavirus infection | MESH:D018352 |
869 | 2118-2126 | Disease | denotes | COVID-19 | MESH:C000657245 |
876 | 3142-3151 | Species | denotes | SARS-CoV2 | Tax:2697049 |
877 | 2810-2819 | Species | denotes | Influenza | Tax:11309 |
878 | 3001-3012 | Chemical | denotes | baricitinib | MESH:C000596027 |
879 | 2314-2323 | Disease | denotes | infection | MESH:D007239 |
880 | 2525-2533 | Disease | denotes | infected | MESH:D007239 |
881 | 3152-3161 | Disease | denotes | infection | MESH:D007239 |
886 | 3250-3261 | Chemical | denotes | baricitinib | MESH:C000596027 |
887 | 3282-3290 | Disease | denotes | COVID-19 | MESH:C000657245 |
888 | 3291-3300 | Disease | denotes | infection | MESH:D007239 |
889 | 3443-3458 | Disease | denotes | viral pneumonia |
LitCovid-PD-FMA-UBERON
Id | Subject | Object | Predicate | Lexical cue | fma_id |
---|---|---|---|---|---|
T100 | 91-96 | Body_part | denotes | cells | http://purl.org/sig/ont/fma/fma68646 |
T101 | 178-186 | Body_part | denotes | clathrin | http://purl.org/sig/ont/fma/fma62262 |
T102 | 287-294 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T103 | 412-416 | Body_part | denotes | lung | http://purl.org/sig/ont/fma/fma7195 |
T104 | 417-422 | Body_part | denotes | cells | http://purl.org/sig/ont/fma/fma68646 |
T105 | 713-718 | Body_part | denotes | cells | http://purl.org/sig/ont/fma/fma68646 |
T106 | 1100-1106 | Body_part | denotes | plasma | http://purl.org/sig/ont/fma/fma62970 |
T107 | 2058-2066 | Body_part | denotes | clathrin | http://purl.org/sig/ont/fma/fma62262 |
T108 | 2534-2539 | Body_part | denotes | cells | http://purl.org/sig/ont/fma/fma68646 |
LitCovid-PD-UBERON
Id | Subject | Object | Predicate | Lexical cue | uberon_id |
---|---|---|---|---|---|
T28 | 412-416 | Body_part | denotes | lung | http://purl.obolibrary.org/obo/UBERON_0002048 |
LitCovid_AGAC
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
p51685s7 | 2838-2856 | Pathway | denotes | JAK/STAT signaling |
p51685s12 | 2860-2868 | NegReg | denotes | reducing |
p51685s14 | 2873-2883 | MPA | denotes | expression |
p51685s22 | 2920-2930 | NegReg | denotes | inhibiting |
p51685s23 | 2931-2944 | Pathway | denotes | IFN signaling |
p51686s18 | 3053-3081 | MPA | denotes | mediated anti-viral response |
LitCovid-PD-MONDO
Id | Subject | Object | Predicate | Lexical cue | mondo_id |
---|---|---|---|---|---|
T290 | 64-72 | Disease | denotes | SARS-CoV | http://purl.obolibrary.org/obo/MONDO_0005091 |
T291 | 700-709 | Disease | denotes | infection | http://purl.obolibrary.org/obo/MONDO_0005550 |
T292 | 722-728 | Disease | denotes | Dengue | http://purl.obolibrary.org/obo/MONDO_0005502 |
T293 | 736-741 | Disease | denotes | Ebola | http://purl.obolibrary.org/obo/MONDO_0005737 |
T294 | 1176-1178 | Disease | denotes | RA | http://purl.obolibrary.org/obo/MONDO_0005272|http://purl.obolibrary.org/obo/MONDO_0008383 |
T296 | 1351-1354 | Disease | denotes | CRS | http://purl.obolibrary.org/obo/MONDO_0007399|http://purl.obolibrary.org/obo/MONDO_0017361 |
T298 | 1447-1456 | Disease | denotes | pneumonia | http://purl.obolibrary.org/obo/MONDO_0005249 |
T299 | 1464-1472 | Disease | denotes | COVID-19 | http://purl.obolibrary.org/obo/MONDO_0100096 |
T300 | 1909-1911 | Disease | denotes | RA | http://purl.obolibrary.org/obo/MONDO_0005272|http://purl.obolibrary.org/obo/MONDO_0008383 |
T302 | 1976-1985 | Disease | denotes | infection | http://purl.obolibrary.org/obo/MONDO_0005550 |
T303 | 2118-2126 | Disease | denotes | COVID-19 | http://purl.obolibrary.org/obo/MONDO_0100096 |
T304 | 2314-2323 | Disease | denotes | infection | http://purl.obolibrary.org/obo/MONDO_0005550 |
T305 | 2810-2819 | Disease | denotes | Influenza | http://purl.obolibrary.org/obo/MONDO_0005812 |
T306 | 3142-3146 | Disease | denotes | SARS | http://purl.obolibrary.org/obo/MONDO_0005091 |
T307 | 3152-3161 | Disease | denotes | infection | http://purl.obolibrary.org/obo/MONDO_0005550 |
T308 | 3282-3290 | Disease | denotes | COVID-19 | http://purl.obolibrary.org/obo/MONDO_0100096 |
T309 | 3291-3300 | Disease | denotes | infection | http://purl.obolibrary.org/obo/MONDO_0005550 |
T310 | 3443-3458 | Disease | denotes | viral pneumonia | http://purl.obolibrary.org/obo/MONDO_0006012 |
T311 | 3449-3458 | Disease | denotes | pneumonia | http://purl.obolibrary.org/obo/MONDO_0005249 |
LitCovid-PD-CLO
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T200 | 91-96 | http://purl.obolibrary.org/obo/GO_0005623 | denotes | cells |
T201 | 343-346 | http://purl.obolibrary.org/obo/CLO_0037126 | denotes | GAK |
T202 | 401-406 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | virus |
T203 | 412-416 | http://purl.obolibrary.org/obo/UBERON_0002048 | denotes | lung |
T204 | 412-416 | http://www.ebi.ac.uk/efo/EFO_0000934 | denotes | lung |
T205 | 417-422 | http://purl.obolibrary.org/obo/GO_0005623 | denotes | cells |
T206 | 462-467 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | virus |
T207 | 479-482 | http://purl.obolibrary.org/obo/CLO_0054060 | denotes | 102 |
T208 | 713-718 | http://purl.obolibrary.org/obo/GO_0005623 | denotes | cells |
T209 | 729-734 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | virus |
T210 | 742-747 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | virus |
T211 | 775-780 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | virus |
T212 | 1089-1092 | http://purl.obolibrary.org/obo/CLO_0037126 | denotes | GAK |
T213 | 1100-1106 | http://purl.obolibrary.org/obo/UBERON_0001969 | denotes | plasma |
T214 | 1217-1218 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T215 | 1375-1391 | http://purl.obolibrary.org/obo/PR_000000017 | denotes | interferon gamma |
T216 | 1595-1596 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T217 | 1898-1904 | http://purl.obolibrary.org/obo/UBERON_0000473 | denotes | tested |
T218 | 2335-2345 | http://purl.obolibrary.org/obo/CLO_0001658 | denotes | activation |
T219 | 2380-2389 | http://purl.obolibrary.org/obo/SO_0000418 | denotes | signaling |
T220 | 2465-2470 | http://purl.obolibrary.org/obo/OGG_0000000002 | denotes | genes |
T221 | 2510-2517 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | viruses |
T222 | 2534-2539 | http://purl.obolibrary.org/obo/GO_0005623 | denotes | cells |
T223 | 2558-2565 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | viruses |
T224 | 2660-2669 | http://purl.obolibrary.org/obo/SO_0000418 | denotes | signaling |
T225 | 2820-2821 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | A |
T226 | 2822-2829 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | viruses |
T227 | 2847-2856 | http://purl.obolibrary.org/obo/SO_0000418 | denotes | signaling |
T228 | 2935-2944 | http://purl.obolibrary.org/obo/SO_0000418 | denotes | signaling |
T229 | 2946-2949 | http://purl.obolibrary.org/obo/CLO_0053001 | denotes | 114 |
T230 | 2955-2956 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T231 | 3088-3089 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
LitCovid-PD-CHEBI
Id | Subject | Object | Predicate | Lexical cue | chebi_id |
---|---|---|---|---|---|
T212 | 18-28 | Chemical | denotes | inhibitors | http://purl.obolibrary.org/obo/CHEBI_35222 |
T213 | 287-294 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T214 | 605-614 | Chemical | denotes | erlotinib | http://purl.obolibrary.org/obo/CHEBI_114785 |
T215 | 616-625 | Chemical | denotes | sunitinib | http://purl.obolibrary.org/obo/CHEBI_38940 |
T216 | 627-638 | Chemical | denotes | ruxolitinib | http://purl.obolibrary.org/obo/CHEBI_66919 |
T217 | 1027-1036 | Chemical | denotes | inhibitor | http://purl.obolibrary.org/obo/CHEBI_35222 |
T218 | 1176-1178 | Chemical | denotes | RA | http://purl.obolibrary.org/obo/CHEBI_73810 |
T219 | 1229-1238 | Chemical | denotes | inhibitor | http://purl.obolibrary.org/obo/CHEBI_35222 |
T220 | 1366-1368 | Chemical | denotes | IL | http://purl.obolibrary.org/obo/CHEBI_63895|http://purl.obolibrary.org/obo/CHEBI_74072 |
T222 | 1375-1385 | Chemical | denotes | interferon | http://purl.obolibrary.org/obo/CHEBI_52999 |
T223 | 1386-1391 | Chemical | denotes | gamma | http://purl.obolibrary.org/obo/CHEBI_30212 |
T224 | 1550-1553 | Chemical | denotes | CYP | http://purl.obolibrary.org/obo/CHEBI_38559 |
T225 | 1554-1558 | Chemical | denotes | drug | http://purl.obolibrary.org/obo/CHEBI_23888 |
T226 | 1590-1594 | Chemical | denotes | drug | http://purl.obolibrary.org/obo/CHEBI_23888 |
T227 | 1660-1675 | Chemical | denotes | antiviral drugs | http://purl.obolibrary.org/obo/CHEBI_36044 |
T228 | 1660-1669 | Chemical | denotes | antiviral | http://purl.obolibrary.org/obo/CHEBI_22587 |
T229 | 1670-1675 | Chemical | denotes | drugs | http://purl.obolibrary.org/obo/CHEBI_23888 |
T230 | 1684-1703 | Chemical | denotes | lopinavir/ritonavir | http://purl.obolibrary.org/obo/CHEBI_145924 |
T231 | 1684-1693 | Chemical | denotes | lopinavir | http://purl.obolibrary.org/obo/CHEBI_31781 |
T232 | 1694-1703 | Chemical | denotes | ritonavir | http://purl.obolibrary.org/obo/CHEBI_45409 |
T233 | 1708-1718 | Chemical | denotes | remdesivir | http://purl.obolibrary.org/obo/CHEBI_145994 |
T234 | 1741-1752 | Chemical | denotes | tofacitinib | http://purl.obolibrary.org/obo/CHEBI_71200 |
T235 | 1875-1885 | Chemical | denotes | inhibitors | http://purl.obolibrary.org/obo/CHEBI_35222 |
T236 | 1909-1911 | Chemical | denotes | RA | http://purl.obolibrary.org/obo/CHEBI_73810 |
T237 | 2153-2164 | Chemical | denotes | ruxolitinib | http://purl.obolibrary.org/obo/CHEBI_66919 |
T238 | 2443-2453 | Chemical | denotes | interferon | http://purl.obolibrary.org/obo/CHEBI_52999 |
LitCovid-PD-GO-BP
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T52 | 11-28 | http://purl.obolibrary.org/obo/GO_0033673 | denotes | kinase inhibitors |
T53 | 105-134 | http://purl.obolibrary.org/obo/GO_0006898 | denotes | receptor-mediated endocytosis |
T54 | 123-134 | http://purl.obolibrary.org/obo/GO_0006897 | denotes | endocytosis |
T55 | 164-207 | http://purl.obolibrary.org/obo/GO_2000369 | denotes | regulators of clathrin-mediated endocytosis |
T56 | 178-207 | http://purl.obolibrary.org/obo/GO_0072583 | denotes | clathrin-mediated endocytosis |
T57 | 196-207 | http://purl.obolibrary.org/obo/GO_0006897 | denotes | endocytosis |
T58 | 315-321 | http://purl.obolibrary.org/obo/GO_0016538 | denotes | cyclin |
T59 | 1322-1343 | http://purl.obolibrary.org/obo/GO_0006954 | denotes | inflammatory response |
T60 | 2058-2087 | http://purl.obolibrary.org/obo/GO_0072583 | denotes | clathrin-mediated endocytosis |
T61 | 2076-2087 | http://purl.obolibrary.org/obo/GO_0006897 | denotes | endocytosis |
T62 | 2234-2257 | http://purl.obolibrary.org/obo/GO_0045087 | denotes | innate immune responses |
T63 | 2269-2286 | http://purl.obolibrary.org/obo/GO_0019079 | denotes | viral replication |
T64 | 2269-2286 | http://purl.obolibrary.org/obo/GO_0019058 | denotes | viral replication |
T65 | 2349-2362 | http://purl.obolibrary.org/obo/GO_0006351 | denotes | transcription |
T66 | 2375-2397 | http://purl.obolibrary.org/obo/GO_0097696 | denotes | STAT signaling pathway |
T67 | 2380-2397 | http://purl.obolibrary.org/obo/GO_0007165 | denotes | signaling pathway |
T68 | 2380-2389 | http://purl.obolibrary.org/obo/GO_0023052 | denotes | signaling |
T69 | 2660-2677 | http://purl.obolibrary.org/obo/GO_0007165 | denotes | signaling pathway |
T70 | 2660-2669 | http://purl.obolibrary.org/obo/GO_0023052 | denotes | signaling |
T71 | 2778-2787 | http://purl.obolibrary.org/obo/GO_0016032 | denotes | virulence |
T72 | 2778-2787 | http://purl.obolibrary.org/obo/GO_0009405 | denotes | virulence |
T73 | 2847-2856 | http://purl.obolibrary.org/obo/GO_0023052 | denotes | signaling |
T74 | 2935-2944 | http://purl.obolibrary.org/obo/GO_0023052 | denotes | signaling |
LitCovid-sentences
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T146 | 0-28 | Sentence | denotes | 5.4 Janus kinase inhibitors |
T147 | 29-140 | Sentence | denotes | As previously described in detail, SARS-CoV-2 enters targeted cells through receptor-mediated endocytosis [12]. |
T148 | 141-354 | Sentence | denotes | Some of the identified regulators of clathrin-mediated endocytosis are members of the numb-associated kinase (NAK) family, such as AP2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK) [101]. |
T149 | 355-484 | Sentence | denotes | Inhibition of AAK1 may stop the access of the virus into lung cells and also the intracellular assembly of virus particles [102]. |
T150 | 485-565 | Sentence | denotes | Of 47 AAK1 blockers approved for medical use, 6 inhibit AAK1 with high affinity. |
T151 | 566-787 | Sentence | denotes | These include oncologic agents such as erlotinib, sunitinib, ruxolitinib, and fedratinib, which have all been demonstrated to inhibit infection of cells by Dengue virus, Ebola virus, and respiratory syncytial virus [103]. |
T152 | 788-1006 | Sentence | denotes | Unfortunately, all these compounds are able to produce adequate NAK inhibition only at doses significantly higher than those normally used in clinical practice and therefore potentially toxic for the patient [104,105]. |
T153 | 1007-1203 | Sentence | denotes | Conversely, the JAK inhibitor baricitinib is able to effectively inhibit AAK1 and GAK at the plasma concentration obtained with the approved dosage for the treatment of RA (2 to 4 mg daily) [106]. |
T154 | 1204-1483 | Sentence | denotes | Moreover, as a selective inhibitor of JAK 1 and 2, baricitinib is also able to produce an important dampening of host inflammatory response due to CRS (including IL-6 and interferon gamma) responsible for the more severe forms of interstitial pneumonia during COVID-19 [107,108]. |
T155 | 1484-1725 | Sentence | denotes | Finally, the minimal interaction of baricitinib with the relevant CYP drug-metabolising enzymes makes the drug a possible candidate for inclusion in combination protocols with antiviral drugs such as lopinavir/ritonavir and remdesivir [109]. |
T156 | 1726-1986 | Sentence | denotes | Interestingly, tofacitinib shows no detectable inhibition of AAK1 [104], whereas currently no data are available on the possible effect of other JAK inhibitors approved or tested for RA (such as upadacitinib or filgotinib) in relation to coronavirus infection. |
T157 | 1987-2184 | Sentence | denotes | Unexpectedly, the only clinical trial evaluating the potential role of clathrin-mediated endocytosis blockade in the management of COVID-19 is currently ongoing with ruxolitinib (ChiCTR2000029580). |
T158 | 2185-2330 | Sentence | denotes | On the other side, IFN is one of the most potent innate immune responses to prevent viral replication during the early phases of infection [110]. |
T159 | 2331-2546 | Sentence | denotes | The activation of transcription through JAK/STAT signaling pathway by IFNs leads to the upregulation of several interferon stimulated genes which have the ability to rapidly kill viruses within infected cells [111]. |
T160 | 2547-2794 | Sentence | denotes | Almost all viruses have developed strategies to combat the effects of type 1 and type 3 IFNs by blocking the IFN signaling pathway [112] and viral encoded factors able to antagonize the JAK/STAT pathway are crucial determinants of virulence [113]. |
T161 | 2795-2951 | Sentence | denotes | In particular, Influenza A viruses disrupt JAK/STAT signaling by reducing the expression of the IFN receptor and by directly inhibiting IFN signaling [114]. |
T162 | 2952-3202 | Sentence | denotes | As a consequence, JAK/STAT blockade generated by baricitinib certainly produces an impairment of IFN-mediated anti-viral response, with a potential facilitating effect on the progression of SARS-CoV2 infection at the moment not yet better quantified. |
T163 | 3203-3459 | Sentence | denotes | In conclusion, evidence of the possible use of baricitinib in the treatment of COVID-19 infection remains highly controversial and further studies are warranted to better clarify its potential role in the treatment of more serious cases of viral pneumonia. |
LitCovid-PD-HP
Id | Subject | Object | Predicate | Lexical cue | hp_id |
---|---|---|---|---|---|
T83 | 1176-1178 | Phenotype | denotes | RA | http://purl.obolibrary.org/obo/HP_0001370 |
T84 | 1447-1456 | Phenotype | denotes | pneumonia | http://purl.obolibrary.org/obo/HP_0002090 |
T85 | 1909-1911 | Phenotype | denotes | RA | http://purl.obolibrary.org/obo/HP_0001370 |
T86 | 3449-3458 | Phenotype | denotes | pneumonia | http://purl.obolibrary.org/obo/HP_0002090 |
2_test
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
32205186-28240606-4826922 | 782-785 | 28240606 | denotes | 103 |
32205186-29753658-4826923 | 1001-1004 | 29753658 | denotes | 105 |
32205186-29545548-4826924 | 1474-1477 | 29545548 | denotes | 107 |
32205186-29649002-4826925 | 1478-1481 | 29649002 | denotes | 108 |
32205186-18049472-4826926 | 2325-2328 | 18049472 | denotes | 110 |