
PMC:7094172 / 24048-28114
Annnotations
LitCovid-PMC-OGER-BB
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T406 | 2056-2064 | SP_9 | denotes | MERS-CoV |
T405 | 2250-2263 | NCBITaxon:11118 | denotes | coronaviruses |
T404 | 2454-2463 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T403 | 2537-2545 | SP_7 | denotes | COVID-19 |
T402 | 2568-2573 | NCBITaxon:10088 | denotes | mouse |
T401 | 2574-2583 | NCBITaxon:5690 | denotes | hepatitis |
T400 | 2584-2589 | NCBITaxon:10239 | denotes | virus |
T399 | 2591-2594 | NCBITaxon:11757 | denotes | MHV |
T398 | 2624-2629 | NCBITaxon:10239 | denotes | viral |
T397 | 2673-2676 | NCBITaxon:11757 | denotes | MHV |
T396 | 2677-2688 | GO:0006260 | denotes | replication |
T395 | 3479-3488 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T394 | 3622-3633 | GO:0051259 | denotes | oligomerize |
T393 | 3645-3653 | SP_9 | denotes | MERS-CoV |
T392 | 3654-3663 | PG_4 | denotes | N protein |
T391 | 3749-3757 | CHEBI:36357;CHEBI:36357 | denotes | molecule |
T390 | 3960-3964 | CHEBI:23888;CHEBI:23888 | denotes | drug |
T389 | 4030-4039 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T424 | 44-53 | CHEBI:36357;CHEBI:36357 | denotes | molecules |
T423 | 167-176 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T422 | 330-339 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T421 | 582-595 | PG_4 | denotes | nucleoprotein |
T420 | 671-680 | CHEBI:25106;CHEBI:25106 | denotes | macrolide |
T419 | 712-730 | GO:0015629 | denotes | actin cytoskeleton |
T418 | 745-755 | CHEBI:67079;CHEBI:67079 | denotes | anticancer |
T417 | 816-817 | GO:0000811 | denotes | G |
T416 | 817-823 | GO:0031941 | denotes | -actin |
T415 | 1296-1314 | CHEBI:36357;CHEBI:36357 | denotes | molecule compounds |
T414 | 1562-1570 | SP_9 | denotes | MERS-CoV |
T413 | 1613-1621 | SP_9 | denotes | MERS-CoV |
T412 | 1628-1640 | GO:0046983 | denotes | dimerization |
T411 | 1658-1667 | PG_4 | denotes | N protein |
T410 | 1767-1770 | SO:0000694 | denotes | RNP |
T409 | 1997-2001 | CHEBI:23888;CHEBI:23888;GO:0017144 | denotes | drug |
T408 | 2002-2013 | GO:0017144 | denotes | development |
T407 | 2034-2047 | NCBITaxon:11118 | denotes | coronaviruses |
LitCovid-PD-FMA-UBERON
Id | Subject | Object | Predicate | Lexical cue | fma_id |
---|---|---|---|---|---|
T121 | 712-730 | Body_part | denotes | actin cytoskeleton | http://purl.org/sig/ont/fma/fma84684 |
T122 | 816-823 | Body_part | denotes | G-actin | http://purl.org/sig/ont/fma/fma67893 |
T123 | 968-975 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T124 | 976-983 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T125 | 988-995 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T126 | 1506-1513 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T127 | 1660-1667 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T128 | 1969-1977 | Body_part | denotes | proteins | http://purl.org/sig/ont/fma/fma67257 |
T129 | 2070-2081 | Body_part | denotes | amino acids | http://purl.org/sig/ont/fma/fma82739 |
T130 | 2715-2719 | Body_part | denotes | hand | http://purl.org/sig/ont/fma/fma9712 |
T131 | 3104-3111 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T132 | 3602-3610 | Body_part | denotes | proteins | http://purl.org/sig/ont/fma/fma67257 |
T133 | 3656-3663 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
LitCovid-PD-UBERON
Id | Subject | Object | Predicate | Lexical cue | uberon_id |
---|---|---|---|---|---|
T2 | 2715-2719 | Body_part | denotes | hand | http://purl.obolibrary.org/obo/UBERON_0002398 |
LitCovid_AGAC
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
p35904s12 | 700-707 | NegReg | denotes | disrupt |
p35904s14 | 712-730 | MPA | denotes | actin cytoskeleton |
p35911s11 | 1649-1679 | MPA | denotes | abnormal N protein aggregation |
p35918s15 | 2611-2620 | NegReg | denotes | reduction |
LitCovid-PD-MONDO
Id | Subject | Object | Predicate | Lexical cue | mondo_id |
---|---|---|---|---|---|
T92 | 452-461 | Disease | denotes | influenza | http://purl.obolibrary.org/obo/MONDO_0005812 |
T93 | 1624-1627 | Disease | denotes | NTD | http://purl.obolibrary.org/obo/MONDO_0008449|http://purl.obolibrary.org/obo/MONDO_0018075 |
T95 | 2135-2138 | Disease | denotes | NTD | http://purl.obolibrary.org/obo/MONDO_0008449|http://purl.obolibrary.org/obo/MONDO_0018075 |
T97 | 2537-2545 | Disease | denotes | COVID-19 | http://purl.obolibrary.org/obo/MONDO_0100096 |
T98 | 2574-2583 | Disease | denotes | hepatitis | http://purl.obolibrary.org/obo/MONDO_0002251 |
LitCovid-PD-CLO
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T181 | 82-85 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
T182 | 103-104 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T183 | 299-301 | http://purl.obolibrary.org/obo/CLO_0001000 | denotes | 35 |
T184 | 512-513 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T185 | 649-653 | http://purl.obolibrary.org/obo/CLO_0001627 | denotes | A, a |
T186 | 682-685 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
T187 | 775-778 | http://purl.obolibrary.org/obo/CLO_0050884 | denotes | ten |
T188 | 827-828 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T189 | 858-860 | http://purl.obolibrary.org/obo/CLO_0053794 | denotes | 41 |
T190 | 939-940 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T191 | 1196-1204 | http://purl.obolibrary.org/obo/CLO_0009985 | denotes | focusing |
T192 | 1367-1368 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T193 | 1439-1440 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T194 | 1483-1491 | http://purl.obolibrary.org/obo/CLO_0001658 | denotes | activity |
T195 | 1878-1881 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
T196 | 1991-1992 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T197 | 2484-2492 | http://purl.obolibrary.org/obo/CLO_0001658 | denotes | activity |
T198 | 2501-2502 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T199 | 2555-2561 | http://purl.obolibrary.org/obo/UBERON_0000473 | denotes | tested |
T200 | 2568-2573 | http://purl.obolibrary.org/obo/CLO_0007836 | denotes | mouse |
T201 | 2584-2589 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | virus |
T202 | 2609-2610 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T203 | 2697-2699 | http://purl.obolibrary.org/obo/CLO_0008933 | denotes | S5 |
T204 | 3319-3321 | http://purl.obolibrary.org/obo/CLO_0007874 | denotes | MS |
T205 | 3322-3324 | http://purl.obolibrary.org/obo/CLO_0053799 | denotes | 45 |
T206 | 3938-3944 | http://purl.obolibrary.org/obo/UBERON_0000473 | denotes | tested |
LitCovid-PD-CHEBI
Id | Subject | Object | Predicate | Lexical cue | chebi_id |
---|---|---|---|---|---|
T200 | 44-53 | Chemical | denotes | molecules | http://purl.obolibrary.org/obo/CHEBI_25367 |
T201 | 67-70 | Chemical | denotes | PPI | http://purl.obolibrary.org/obo/CHEBI_53266|http://purl.obolibrary.org/obo/CHEBI_60614 |
T203 | 229-232 | Chemical | denotes | PPI | http://purl.obolibrary.org/obo/CHEBI_53266|http://purl.obolibrary.org/obo/CHEBI_60614 |
T205 | 393-396 | Chemical | denotes | PPI | http://purl.obolibrary.org/obo/CHEBI_53266|http://purl.obolibrary.org/obo/CHEBI_60614 |
T207 | 596-605 | Chemical | denotes | oligomers | http://purl.obolibrary.org/obo/CHEBI_132554 |
T208 | 671-680 | Chemical | denotes | macrolide | http://purl.obolibrary.org/obo/CHEBI_25106 |
T209 | 745-761 | Chemical | denotes | anticancer agent | http://purl.obolibrary.org/obo/CHEBI_35610 |
T210 | 968-975 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T211 | 976-983 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T212 | 988-995 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T213 | 996-1002 | Chemical | denotes | ligand | http://purl.obolibrary.org/obo/CHEBI_52214 |
T214 | 1265-1271 | Chemical | denotes | ligand | http://purl.obolibrary.org/obo/CHEBI_52214 |
T215 | 1296-1304 | Chemical | denotes | molecule | http://purl.obolibrary.org/obo/CHEBI_25367 |
T216 | 1506-1513 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T217 | 1660-1667 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T218 | 1969-1977 | Chemical | denotes | proteins | http://purl.obolibrary.org/obo/CHEBI_36080 |
T219 | 1997-2001 | Chemical | denotes | drug | http://purl.obolibrary.org/obo/CHEBI_23888 |
T220 | 2070-2081 | Chemical | denotes | amino acids | http://purl.obolibrary.org/obo/CHEBI_33709 |
T221 | 2070-2075 | Chemical | denotes | amino | http://purl.obolibrary.org/obo/CHEBI_46882 |
T222 | 2076-2081 | Chemical | denotes | acids | http://purl.obolibrary.org/obo/CHEBI_37527 |
T223 | 2384-2386 | Chemical | denotes | S4 | http://purl.obolibrary.org/obo/CHEBI_29401 |
T224 | 2697-2699 | Chemical | denotes | S5 | http://purl.obolibrary.org/obo/CHEBI_29386 |
T225 | 2877-2880 | Chemical | denotes | PPI | http://purl.obolibrary.org/obo/CHEBI_53266|http://purl.obolibrary.org/obo/CHEBI_60614 |
T227 | 3104-3111 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T228 | 3291-3299 | Chemical | denotes | hydrogen | http://purl.obolibrary.org/obo/CHEBI_49637 |
T229 | 3300-3309 | Chemical | denotes | deuterium | http://purl.obolibrary.org/obo/CHEBI_29237 |
T230 | 3319-3321 | Chemical | denotes | MS | http://purl.obolibrary.org/obo/CHEBI_73613 |
T231 | 3602-3610 | Chemical | denotes | proteins | http://purl.obolibrary.org/obo/CHEBI_36080 |
T232 | 3656-3663 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T233 | 3749-3757 | Chemical | denotes | molecule | http://purl.obolibrary.org/obo/CHEBI_25367 |
T234 | 3960-3964 | Chemical | denotes | drug | http://purl.obolibrary.org/obo/CHEBI_23888 |
T235 | 4025-4039 | Chemical | denotes | lead compounds | http://purl.obolibrary.org/obo/CHEBI_33585 |
LitCovid-PD-GO-BP
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T19 | 1710-1718 | http://purl.obolibrary.org/obo/GO_0007610 | denotes | behavior |
T20 | 1771-1780 | http://purl.obolibrary.org/obo/GO_0009058 | denotes | formation |
T21 | 2794-2803 | http://purl.obolibrary.org/obo/GO_0009058 | denotes | formation |
T22 | 3310-3318 | http://purl.obolibrary.org/obo/GO_0015297 | denotes | exchange |
LitCovid-PD-HP
Id | Subject | Object | Predicate | Lexical cue | hp_id |
---|---|---|---|---|---|
T4 | 2574-2583 | Phenotype | denotes | hepatitis | http://purl.obolibrary.org/obo/HP_0012115 |
LitCovid-sentences
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T193 | 0-26 | Sentence | denotes | Discussion and Conclusions |
T194 | 27-161 | Sentence | denotes | The use of small molecules to stabilize PPI interfaces has been shown to be a viable approach for the development of new therapeutics. |
T195 | 162-1153 | Sentence | denotes | Most compounds created by structure-based design to manipulate the PPI depend on detailed knowledge of the native interacting interfaces.35−37 In contrast, most of the compounds with therapeutic potential that stabilize non-native PPI interfaces were discovered by chance alone.38 The anti-influenza compound nucleozin was initially discovered using a chemical genetics approach, and its ability to stabilize non-native nucleoprotein oligomers was elucidated much later.39,40 Swinholide A, a cytotoxic marine macrolide, has been known to disrupt the actin cytoskeleton and act as an anticancer agent, but it took ten years to discover that it stabilized G-actin as a non-native homodimer complex.41−43 However, these examples did underscore the importance of hydrophobicity as a crucial factor stabilizing protein–protein and protein–ligand associations.44 Here, we demonstrated the possibility of using the hydrophobic interactions on non-native interfaces as targets for virtual screening. |
T196 | 1154-1385 | Sentence | denotes | Combined with suitable selection criteria focusing on both shape and hydrophobic complementarities between the ligand and the receptor, small-molecule compounds that stabilize non-native PPIs may be identified in a rational manner. |
T197 | 1386-1589 | Sentence | denotes | Using the above approach, we successfully identified a compound P3 that affected the biochemical activity of our target protein and showed efficacy against our target pathogen MERS-CoV (Figures 2 and 4). |
T198 | 1590-1781 | Sentence | denotes | P3-mediated non-native MERS-CoV N-NTD dimerization induced abnormal N protein aggregation by influencing the oligomeric behavior of N-CTD and eventually halting its function in RNP formation. |
T199 | 1782-1925 | Sentence | denotes | To the best of our knowledge, this structure-based strategy for targeting non-native interfaces has never been proposed for therapeutic design. |
T200 | 1926-2027 | Sentence | denotes | Thus, non-native interaction interfaces in proteins may comprise a new drug development target class. |
T201 | 2028-2164 | Sentence | denotes | For β-coronaviruses such as MERS-CoV, the amino acids comprising the non-native interaction interface on N-NTD are relatively conserved. |
T202 | 2165-2388 | Sentence | denotes | The hydrophobic pocket surrounding W43 and F135 on monomer 1 is shared among other β-coronaviruses.24,28 The interacting surface on monomer 2, which includes G104, T105, G106, and A109, is also highly conserved (Figure S4). |
T203 | 2389-2546 | Sentence | denotes | This conservation may provide certain advantages when developing compounds with broad-spectrum activity against a target pathogen family, including COVID-19. |
T204 | 2547-2701 | Sentence | denotes | When we tested P3 on mouse hepatitis virus (MHV), we observed a reduction in viral titer, indicating that P3 may also inhibit MHV replication (Figure S5). |
T205 | 2702-2780 | Sentence | denotes | On the other hand, targeting non-native interaction interfaces is not trivial. |
T206 | 2781-2952 | Sentence | denotes | As interface formation is induced by an external agent, computations aimed at predicting native PPI structures may not be able to identify potential non-native interfaces. |
T207 | 2953-3066 | Sentence | denotes | Nevertheless, several stratagems may assist in the identification of potential non-native interaction interfaces. |
T208 | 3067-3189 | Sentence | denotes | One strategy is to search for target protein structures with crystal packing contacts known to be biologically irrelevant. |
T209 | 3190-3516 | Sentence | denotes | Another approach is to identify weakly interacting sites through NMR chemical shift perturbation and hydrogen-deuterium exchange MS.45 Once these potential non-native interaction interfaces are identified, standard screening and then functional characterization may be conducted for small compounds that bind to the interface. |
T210 | 3517-3634 | Sentence | denotes | To summarize, we demonstrated that non-native interaction interfaces might form when proteins abnormally oligomerize. |
T211 | 3635-3785 | Sentence | denotes | Using the MERS-CoV N protein as an example, we showed that non-native interfaces might serve as targets for small-molecule, structure-based screening. |
T212 | 3786-3898 | Sentence | denotes | We also proposed several stratagems to rationally identify potential non-native interface targets for screening. |
T213 | 3899-4066 | Sentence | denotes | We believe that we have discovered and tested an alternative drug discovery paradigm that could help expand the repertoire of lead compounds against various pathogens. |
LitCovid-PubTator
Id | Subject | Object | Predicate | Lexical cue | tao:has_database_id |
---|---|---|---|---|---|
418 | 1767-1770 | Gene | denotes | RNP | Gene:55599 |
419 | 1562-1570 | Species | denotes | MERS-CoV | Tax:1335626 |
420 | 1613-1621 | Species | denotes | MERS-CoV | Tax:1335626 |
421 | 2032-2047 | Species | denotes | β-coronaviruses | Tax:694002 |
422 | 2056-2064 | Species | denotes | MERS-CoV | Tax:1335626 |
423 | 2248-2263 | Species | denotes | β-coronaviruses | Tax:694002 |
424 | 2568-2589 | Species | denotes | mouse hepatitis virus | Tax:11138 |
425 | 452-461 | Species | denotes | influenza | Tax:11309 |
426 | 2591-2594 | Species | denotes | MHV | Tax:11138 |
427 | 2673-2676 | Species | denotes | MHV | Tax:11138 |
428 | 471-480 | Chemical | denotes | nucleozin | |
429 | 664-680 | Chemical | denotes | marine macrolide | |
430 | 1722-1727 | Chemical | denotes | N-CTD | |
431 | 2133-2138 | Chemical | denotes | N-NTD | |
432 | 3291-3299 | Chemical | denotes | hydrogen | MESH:D006859 |
433 | 3300-3309 | Chemical | denotes | deuterium | MESH:D003903 |
434 | 1649-1679 | Disease | denotes | abnormal N protein aggregation | MESH:D001791 |
435 | 2537-2545 | Disease | denotes | COVID-19 | MESH:C000657245 |
437 | 3645-3653 | Species | denotes | MERS-CoV | Tax:1335626 |
2_test
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
32105468-31141413-61929515 | 299-301 | 31141413 | denotes | 35 |
32105468-28300404-61929516 | 302-304 | 28300404 | denotes | 37 |
32105468-27820802-61929517 | 440-442 | 27820802 | denotes | 38 |
32105468-20512121-61929518 | 635-637 | 20512121 | denotes | 40 |
32105468-15797212-61929519 | 858-860 | 15797212 | denotes | 41 |
32105468-7876075-61929520 | 861-863 | 7876075 | denotes | 43 |
32105468-29308120-61929521 | 1016-1018 | 29308120 | denotes | 44 |
32105468-16775348-61929522 | 2267-2269 | 16775348 | denotes | 28 |
32105468-16503614-61929523 | 3322-3324 | 16503614 | denotes | 45 |