
PMC:7094172 / 24075-27564
Annnotations
LitCovid-PMC-OGER-BB
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T406 | 2029-2037 | SP_9 | denotes | MERS-CoV |
T405 | 2223-2236 | NCBITaxon:11118 | denotes | coronaviruses |
T404 | 2427-2436 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T403 | 2510-2518 | SP_7 | denotes | COVID-19 |
T402 | 2541-2546 | NCBITaxon:10088 | denotes | mouse |
T401 | 2547-2556 | NCBITaxon:5690 | denotes | hepatitis |
T400 | 2557-2562 | NCBITaxon:10239 | denotes | virus |
T399 | 2564-2567 | NCBITaxon:11757 | denotes | MHV |
T398 | 2597-2602 | NCBITaxon:10239 | denotes | viral |
T397 | 2646-2649 | NCBITaxon:11757 | denotes | MHV |
T396 | 2650-2661 | GO:0006260 | denotes | replication |
T395 | 3452-3461 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T424 | 17-26 | CHEBI:36357;CHEBI:36357 | denotes | molecules |
T423 | 140-149 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T422 | 303-312 | CHEBI:36357;CHEBI:36357 | denotes | compounds |
T421 | 555-568 | PG_4 | denotes | nucleoprotein |
T420 | 644-653 | CHEBI:25106;CHEBI:25106 | denotes | macrolide |
T419 | 685-703 | GO:0015629 | denotes | actin cytoskeleton |
T418 | 718-728 | CHEBI:67079;CHEBI:67079 | denotes | anticancer |
T417 | 789-790 | GO:0000811 | denotes | G |
T416 | 790-796 | GO:0031941 | denotes | -actin |
T415 | 1269-1287 | CHEBI:36357;CHEBI:36357 | denotes | molecule compounds |
T414 | 1535-1543 | SP_9 | denotes | MERS-CoV |
T413 | 1586-1594 | SP_9 | denotes | MERS-CoV |
T412 | 1601-1613 | GO:0046983 | denotes | dimerization |
T411 | 1631-1640 | PG_4 | denotes | N protein |
T410 | 1740-1743 | SO:0000694 | denotes | RNP |
T409 | 1970-1974 | CHEBI:23888;CHEBI:23888;GO:0017144 | denotes | drug |
T408 | 1975-1986 | GO:0017144 | denotes | development |
T407 | 2007-2020 | NCBITaxon:11118 | denotes | coronaviruses |
LitCovid-PD-FMA-UBERON
Id | Subject | Object | Predicate | Lexical cue | fma_id |
---|---|---|---|---|---|
T121 | 685-703 | Body_part | denotes | actin cytoskeleton | http://purl.org/sig/ont/fma/fma84684 |
T122 | 789-796 | Body_part | denotes | G-actin | http://purl.org/sig/ont/fma/fma67893 |
T123 | 941-948 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T124 | 949-956 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T125 | 961-968 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T126 | 1479-1486 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T127 | 1633-1640 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
T128 | 1942-1950 | Body_part | denotes | proteins | http://purl.org/sig/ont/fma/fma67257 |
T129 | 2043-2054 | Body_part | denotes | amino acids | http://purl.org/sig/ont/fma/fma82739 |
T130 | 2688-2692 | Body_part | denotes | hand | http://purl.org/sig/ont/fma/fma9712 |
T131 | 3077-3084 | Body_part | denotes | protein | http://purl.org/sig/ont/fma/fma67257 |
LitCovid-PD-UBERON
Id | Subject | Object | Predicate | Lexical cue | uberon_id |
---|---|---|---|---|---|
T2 | 2688-2692 | Body_part | denotes | hand | http://purl.obolibrary.org/obo/UBERON_0002398 |
LitCovid_AGAC
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
p35904s12 | 673-680 | NegReg | denotes | disrupt |
p35904s14 | 685-703 | MPA | denotes | actin cytoskeleton |
p35911s11 | 1622-1652 | MPA | denotes | abnormal N protein aggregation |
p35918s15 | 2584-2593 | NegReg | denotes | reduction |
LitCovid-PD-MONDO
Id | Subject | Object | Predicate | Lexical cue | mondo_id |
---|---|---|---|---|---|
T92 | 425-434 | Disease | denotes | influenza | http://purl.obolibrary.org/obo/MONDO_0005812 |
T93 | 1597-1600 | Disease | denotes | NTD | http://purl.obolibrary.org/obo/MONDO_0008449|http://purl.obolibrary.org/obo/MONDO_0018075 |
T95 | 2108-2111 | Disease | denotes | NTD | http://purl.obolibrary.org/obo/MONDO_0008449|http://purl.obolibrary.org/obo/MONDO_0018075 |
T97 | 2510-2518 | Disease | denotes | COVID-19 | http://purl.obolibrary.org/obo/MONDO_0100096 |
T98 | 2547-2556 | Disease | denotes | hepatitis | http://purl.obolibrary.org/obo/MONDO_0002251 |
LitCovid-PD-CLO
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T181 | 55-58 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
T182 | 76-77 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T183 | 272-274 | http://purl.obolibrary.org/obo/CLO_0001000 | denotes | 35 |
T184 | 485-486 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T185 | 622-626 | http://purl.obolibrary.org/obo/CLO_0001627 | denotes | A, a |
T186 | 655-658 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
T187 | 748-751 | http://purl.obolibrary.org/obo/CLO_0050884 | denotes | ten |
T188 | 800-801 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T189 | 831-833 | http://purl.obolibrary.org/obo/CLO_0053794 | denotes | 41 |
T190 | 912-913 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T191 | 1169-1177 | http://purl.obolibrary.org/obo/CLO_0009985 | denotes | focusing |
T192 | 1340-1341 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T193 | 1412-1413 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T194 | 1456-1464 | http://purl.obolibrary.org/obo/CLO_0001658 | denotes | activity |
T195 | 1851-1854 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
T196 | 1964-1965 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T197 | 2457-2465 | http://purl.obolibrary.org/obo/CLO_0001658 | denotes | activity |
T198 | 2474-2475 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T199 | 2528-2534 | http://purl.obolibrary.org/obo/UBERON_0000473 | denotes | tested |
T200 | 2541-2546 | http://purl.obolibrary.org/obo/CLO_0007836 | denotes | mouse |
T201 | 2557-2562 | http://purl.obolibrary.org/obo/NCBITaxon_10239 | denotes | virus |
T202 | 2582-2583 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T203 | 2670-2672 | http://purl.obolibrary.org/obo/CLO_0008933 | denotes | S5 |
T204 | 3292-3294 | http://purl.obolibrary.org/obo/CLO_0007874 | denotes | MS |
T205 | 3295-3297 | http://purl.obolibrary.org/obo/CLO_0053799 | denotes | 45 |
LitCovid-PD-CHEBI
Id | Subject | Object | Predicate | Lexical cue | chebi_id |
---|---|---|---|---|---|
T200 | 17-26 | Chemical | denotes | molecules | http://purl.obolibrary.org/obo/CHEBI_25367 |
T201 | 40-43 | Chemical | denotes | PPI | http://purl.obolibrary.org/obo/CHEBI_53266|http://purl.obolibrary.org/obo/CHEBI_60614 |
T203 | 202-205 | Chemical | denotes | PPI | http://purl.obolibrary.org/obo/CHEBI_53266|http://purl.obolibrary.org/obo/CHEBI_60614 |
T205 | 366-369 | Chemical | denotes | PPI | http://purl.obolibrary.org/obo/CHEBI_53266|http://purl.obolibrary.org/obo/CHEBI_60614 |
T207 | 569-578 | Chemical | denotes | oligomers | http://purl.obolibrary.org/obo/CHEBI_132554 |
T208 | 644-653 | Chemical | denotes | macrolide | http://purl.obolibrary.org/obo/CHEBI_25106 |
T209 | 718-734 | Chemical | denotes | anticancer agent | http://purl.obolibrary.org/obo/CHEBI_35610 |
T210 | 941-948 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T211 | 949-956 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T212 | 961-968 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T213 | 969-975 | Chemical | denotes | ligand | http://purl.obolibrary.org/obo/CHEBI_52214 |
T214 | 1238-1244 | Chemical | denotes | ligand | http://purl.obolibrary.org/obo/CHEBI_52214 |
T215 | 1269-1277 | Chemical | denotes | molecule | http://purl.obolibrary.org/obo/CHEBI_25367 |
T216 | 1479-1486 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T217 | 1633-1640 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T218 | 1942-1950 | Chemical | denotes | proteins | http://purl.obolibrary.org/obo/CHEBI_36080 |
T219 | 1970-1974 | Chemical | denotes | drug | http://purl.obolibrary.org/obo/CHEBI_23888 |
T220 | 2043-2054 | Chemical | denotes | amino acids | http://purl.obolibrary.org/obo/CHEBI_33709 |
T221 | 2043-2048 | Chemical | denotes | amino | http://purl.obolibrary.org/obo/CHEBI_46882 |
T222 | 2049-2054 | Chemical | denotes | acids | http://purl.obolibrary.org/obo/CHEBI_37527 |
T223 | 2357-2359 | Chemical | denotes | S4 | http://purl.obolibrary.org/obo/CHEBI_29401 |
T224 | 2670-2672 | Chemical | denotes | S5 | http://purl.obolibrary.org/obo/CHEBI_29386 |
T225 | 2850-2853 | Chemical | denotes | PPI | http://purl.obolibrary.org/obo/CHEBI_53266|http://purl.obolibrary.org/obo/CHEBI_60614 |
T227 | 3077-3084 | Chemical | denotes | protein | http://purl.obolibrary.org/obo/CHEBI_36080 |
T228 | 3264-3272 | Chemical | denotes | hydrogen | http://purl.obolibrary.org/obo/CHEBI_49637 |
T229 | 3273-3282 | Chemical | denotes | deuterium | http://purl.obolibrary.org/obo/CHEBI_29237 |
T230 | 3292-3294 | Chemical | denotes | MS | http://purl.obolibrary.org/obo/CHEBI_73613 |
LitCovid-PD-GO-BP
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T19 | 1683-1691 | http://purl.obolibrary.org/obo/GO_0007610 | denotes | behavior |
T20 | 1744-1753 | http://purl.obolibrary.org/obo/GO_0009058 | denotes | formation |
T21 | 2767-2776 | http://purl.obolibrary.org/obo/GO_0009058 | denotes | formation |
T22 | 3283-3291 | http://purl.obolibrary.org/obo/GO_0015297 | denotes | exchange |
LitCovid-PD-HP
Id | Subject | Object | Predicate | Lexical cue | hp_id |
---|---|---|---|---|---|
T4 | 2547-2556 | Phenotype | denotes | hepatitis | http://purl.obolibrary.org/obo/HP_0012115 |
LitCovid-sentences
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T194 | 0-134 | 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 | 135-1126 | 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 | 1127-1358 | 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 | 1359-1562 | 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 | 1563-1754 | 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 | 1755-1898 | 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 | 1899-2000 | Sentence | denotes | Thus, non-native interaction interfaces in proteins may comprise a new drug development target class. |
T201 | 2001-2137 | 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 | 2138-2361 | 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 | 2362-2519 | Sentence | denotes | This conservation may provide certain advantages when developing compounds with broad-spectrum activity against a target pathogen family, including COVID-19. |
T204 | 2520-2674 | 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 | 2675-2753 | Sentence | denotes | On the other hand, targeting non-native interaction interfaces is not trivial. |
T206 | 2754-2925 | 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 | 2926-3039 | Sentence | denotes | Nevertheless, several stratagems may assist in the identification of potential non-native interaction interfaces. |
T208 | 3040-3162 | Sentence | denotes | One strategy is to search for target protein structures with crystal packing contacts known to be biologically irrelevant. |
T209 | 3163-3489 | 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. |
LitCovid-PubTator
Id | Subject | Object | Predicate | Lexical cue | tao:has_database_id |
---|---|---|---|---|---|
418 | 1740-1743 | Gene | denotes | RNP | Gene:55599 |
419 | 1535-1543 | Species | denotes | MERS-CoV | Tax:1335626 |
420 | 1586-1594 | Species | denotes | MERS-CoV | Tax:1335626 |
421 | 2005-2020 | Species | denotes | β-coronaviruses | Tax:694002 |
422 | 2029-2037 | Species | denotes | MERS-CoV | Tax:1335626 |
423 | 2221-2236 | Species | denotes | β-coronaviruses | Tax:694002 |
424 | 2541-2562 | Species | denotes | mouse hepatitis virus | Tax:11138 |
425 | 425-434 | Species | denotes | influenza | Tax:11309 |
426 | 2564-2567 | Species | denotes | MHV | Tax:11138 |
427 | 2646-2649 | Species | denotes | MHV | Tax:11138 |
428 | 444-453 | Chemical | denotes | nucleozin | |
429 | 637-653 | Chemical | denotes | marine macrolide | |
430 | 1695-1700 | Chemical | denotes | N-CTD | |
431 | 2106-2111 | Chemical | denotes | N-NTD | |
432 | 3264-3272 | Chemical | denotes | hydrogen | MESH:D006859 |
433 | 3273-3282 | Chemical | denotes | deuterium | MESH:D003903 |
434 | 1622-1652 | Disease | denotes | abnormal N protein aggregation | MESH:D001791 |
435 | 2510-2518 | Disease | denotes | COVID-19 | MESH:C000657245 |
2_test
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
32105468-31141413-61929515 | 272-274 | 31141413 | denotes | 35 |
32105468-28300404-61929516 | 275-277 | 28300404 | denotes | 37 |
32105468-27820802-61929517 | 413-415 | 27820802 | denotes | 38 |
32105468-20512121-61929518 | 608-610 | 20512121 | denotes | 40 |
32105468-15797212-61929519 | 831-833 | 15797212 | denotes | 41 |
32105468-7876075-61929520 | 834-836 | 7876075 | denotes | 43 |
32105468-29308120-61929521 | 989-991 | 29308120 | denotes | 44 |
32105468-16775348-61929522 | 2240-2242 | 16775348 | denotes | 28 |
32105468-16503614-61929523 | 3295-3297 | 16503614 | denotes | 45 |