PMC:7571312 / 8398-10191
Annnotations
LitCovid-PD-MONDO
| Id | Subject | Object | Predicate | Lexical cue | mondo_id |
|---|---|---|---|---|---|
| T41 | 44-48 | Disease | denotes | SARS | http://purl.obolibrary.org/obo/MONDO_0005091 |
| T42 | 745-749 | Disease | denotes | SARS | http://purl.obolibrary.org/obo/MONDO_0005091 |
| T43 | 846-850 | Disease | denotes | SARS | http://purl.obolibrary.org/obo/MONDO_0005091 |
| T44 | 993-1001 | Disease | denotes | COVID-19 | http://purl.obolibrary.org/obo/MONDO_0100096 |
| T45 | 1073-1077 | Disease | denotes | SARS | http://purl.obolibrary.org/obo/MONDO_0005091 |
| T46 | 1447-1455 | Disease | denotes | COVID-19 | http://purl.obolibrary.org/obo/MONDO_0100096 |
| T47 | 1563-1567 | Disease | denotes | SARS | http://purl.obolibrary.org/obo/MONDO_0005091 |
| T48 | 1784-1792 | Disease | denotes | COVID-19 | http://purl.obolibrary.org/obo/MONDO_0100096 |
LitCovid-PD-CLO
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T92676 | 209-210 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
| T73055 | 211-218 | http://purl.obolibrary.org/obo/CLO_0009985 | denotes | focused |
| T20789 | 286-288 | http://purl.obolibrary.org/obo/CLO_0008285 | denotes | P1 |
| T9121 | 818-819 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
| T13335 | 1012-1019 | http://purl.obolibrary.org/obo/UBERON_0000473 | denotes | testing |
| T88691 | 1020-1023 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
| T27161 | 1047-1048 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
| T90807 | 1116-1117 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
| T52020 | 1158-1164 | http://purl.obolibrary.org/obo/CLO_0001658 | denotes | active |
| T76337 | 1170-1173 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
| T86009 | 1396-1397 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
| T73832 | 1480-1487 | http://purl.obolibrary.org/obo/CLO_0009985 | denotes | focused |
| T49922 | 1691-1692 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
LitCovid-PD-CHEBI
| Id | Subject | Object | Predicate | Lexical cue | chebi_id |
|---|---|---|---|---|---|
| T103 | 286-288 | Chemical | denotes | P1 | http://purl.obolibrary.org/obo/CHEBI_60949 |
| T104 | 289-295 | Chemical | denotes | lactam | http://purl.obolibrary.org/obo/CHEBI_24995 |
| T105 | 314-321 | Chemical | denotes | methoxy | http://purl.obolibrary.org/obo/CHEBI_32772|http://purl.obolibrary.org/obo/CHEBI_44520 |
| T107 | 322-328 | Chemical | denotes | indole | http://purl.obolibrary.org/obo/CHEBI_16881|http://purl.obolibrary.org/obo/CHEBI_35581 |
| T109 | 337-342 | Chemical | denotes | group | http://purl.obolibrary.org/obo/CHEBI_24433 |
| T110 | 480-485 | Chemical | denotes | amide | http://purl.obolibrary.org/obo/CHEBI_29337|http://purl.obolibrary.org/obo/CHEBI_32988 |
| T112 | 486-494 | Chemical | denotes | carbonyl | http://purl.obolibrary.org/obo/CHEBI_23019 |
| T113 | 648-653 | Chemical | denotes | amide | http://purl.obolibrary.org/obo/CHEBI_29337|http://purl.obolibrary.org/obo/CHEBI_32988 |
| T115 | 681-687 | Chemical | denotes | ketone | http://purl.obolibrary.org/obo/CHEBI_17087 |
| T116 | 731-741 | Chemical | denotes | inhibitors | http://purl.obolibrary.org/obo/CHEBI_35222 |
| T117 | 1056-1065 | Chemical | denotes | inhibitor | http://purl.obolibrary.org/obo/CHEBI_35222 |
| T118 | 1418-1420 | Chemical | denotes | IV | http://purl.obolibrary.org/obo/CHEBI_74327 |
| T119 | 1536-1542 | Chemical | denotes | ketone | http://purl.obolibrary.org/obo/CHEBI_17087 |
| T120 | 1549-1559 | Chemical | denotes | inhibitors | http://purl.obolibrary.org/obo/CHEBI_35222 |
| T121 | 1591-1597 | Chemical | denotes | ligand | http://purl.obolibrary.org/obo/CHEBI_52214 |
| T122 | 1693-1701 | Chemical | denotes | molecule | http://purl.obolibrary.org/obo/CHEBI_25367 |
LitCovid-PD-GO-BP
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T6 | 1242-1259 | http://purl.obolibrary.org/obo/GO_0019079 | denotes | viral replication |
| T7 | 1242-1259 | http://purl.obolibrary.org/obo/GO_0019058 | denotes | viral replication |
LitCovid-sentences
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T41 | 0-195 | Sentence | denotes | Although the structure of 2 in complex with SARS CoV-1 3CLpro is the final product, the above analysis is expected to apply similarly to the more relevant and structurally close transition state. |
| T42 | 196-393 | Sentence | denotes | Accordingly, a focused design strategy aimed at replacing the warhead while retaining the P1 lactam and utilizing the methoxy indole capping group in the early rounds of optimization was initiated. |
| T43 | 394-585 | Sentence | denotes | Specifically, an ideal electrophilic warhead would be bioisosteric, with the scissile amide carbonyl of peptidyl substrates ensuring proper alignment within the oxyanion hole of the protease. |
| T44 | 586-790 | Sentence | denotes | To better mimic the tetrahedral intermediate generated in the amide bond cleavage, we designed ketone-based covalent reversible and irreversible inhibitors of SARS CoV-1 3CLpro, as illustrated by 3 and 4. |
| T45 | 791-978 | Sentence | denotes | Compound 4 was selected as a development candidate for SARS CoV-1 but with the successful public health response that ended the 2003 pandemic, the clinical advancement of 4 was suspended. |
| T46 | 979-1186 | Sentence | denotes | Following the COVID-19 outbreak, testing has demonstrated that 4 is a potent inhibitor of the SARS CoV-2 3CLpro (Ki = 0.27 ± 0.1 nM) and a cocrystal structure with 4 bound in the active site has been solved. |
| T47 | 1187-1456 | Sentence | denotes | In addition to the potent inhibition of the 3CLpro and viral replication of several coronaviruses, 4 possesses solubility as well as metabolic and chemical stability characteristics, which are consistent with a continuous infusion IV therapeutic treatment for COVID-19. |
| T48 | 1457-1793 | Sentence | denotes | We report the research focused on the discovery of reversible and irreversible ketone-based inhibitors of SARS CoV-1 3CLpro employing ligand-protease structures solved by X-ray crystallography, which led to the identification of 4 as a molecule warranting further evaluation for its potential to treat coronaviruses, including COVID-19. |
LitCovid-PubTator
| Id | Subject | Object | Predicate | Lexical cue | tao:has_database_id |
|---|---|---|---|---|---|
| 238 | 44-52 | Species | denotes | SARS CoV | Tax:694009 |
| 239 | 745-753 | Species | denotes | SARS CoV | Tax:694009 |
| 240 | 846-854 | Species | denotes | SARS CoV | Tax:694009 |
| 241 | 1073-1083 | Species | denotes | SARS CoV-2 | Tax:2697049 |
| 242 | 1271-1284 | Species | denotes | coronaviruses | Tax:11118 |
| 243 | 1563-1571 | Species | denotes | SARS CoV | Tax:694009 |
| 244 | 1759-1772 | Species | denotes | coronaviruses | Tax:11118 |
| 245 | 289-295 | Chemical | denotes | lactam | MESH:D007769 |
| 246 | 314-328 | Chemical | denotes | methoxy indole | |
| 247 | 480-485 | Chemical | denotes | amide | MESH:D000577 |
| 248 | 648-653 | Chemical | denotes | amide | MESH:D000577 |
| 249 | 681-687 | Chemical | denotes | ketone | MESH:D007659 |
| 250 | 1536-1542 | Chemical | denotes | ketone | MESH:D007659 |
| 251 | 993-1001 | Disease | denotes | COVID-19 | MESH:C000657245 |
| 252 | 1447-1455 | Disease | denotes | COVID-19 | MESH:C000657245 |
| 253 | 1784-1792 | Disease | denotes | COVID-19 | MESH:C000657245 |