PubMed:28287727
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/28287727","sourcedb":"PubMed","sourceid":"28287727","text":"Michael Acceptor-Based Peptidomimetic Inhibitor of Main Protease from Porcine Epidemic Diarrhea Virus.\nPorcine epidemic diarrhea virus (PEDV) causes high mortality in pigs. PEDV main protease (M(pro)) plays an essential role in viral replication. We solved the structure of PEDV M(pro) complexed with peptidomimetic inhibitor N3 carrying a Michael acceptor warhead, revealing atomic level interactions. We further designed a series of 17 inhibitors with altered side groups. Inhibitors M2 and M17 demonstrated enhanced specificity against PEDV M(pro). These compounds have potential as future therapeutics to combat PEDV infection.","tracks":[{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":103,"end":172},"obj":"DRI_Background"},{"id":"T2","span":{"begin":247,"end":402},"obj":"DRI_Approach"},{"id":"T3","span":{"begin":403,"end":474},"obj":"DRI_Approach"},{"id":"T4","span":{"begin":475,"end":551},"obj":"DRI_Approach"},{"id":"T5","span":{"begin":552,"end":631},"obj":"DRI_FutureWork"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T2","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T3","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T4","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T5","pred":"source","obj":"PubMed_ArguminSci"}]},{"project":"GoldHamster","denotations":[{"id":"T2","span":{"begin":8,"end":16},"obj":"CHEBI:15339"},{"id":"T1","span":{"begin":8,"end":16},"obj":"SO:0000164"},{"id":"T3","span":{"begin":23,"end":37},"obj":"CHEBI:63175"},{"id":"T4","span":{"begin":38,"end":47},"obj":"CHEBI:35222"},{"id":"T5","span":{"begin":56,"end":64},"obj":"P68985"},{"id":"T6","span":{"begin":56,"end":64},"obj":"P30202"},{"id":"T7","span":{"begin":56,"end":64},"obj":"P42672"},{"id":"T8","span":{"begin":56,"end":64},"obj":"P11826"},{"id":"T9","span":{"begin":56,"end":64},"obj":"Q5TJ03"},{"id":"T10","span":{"begin":56,"end":64},"obj":"O71070"},{"id":"T11","span":{"begin":56,"end":64},"obj":"P63122"},{"id":"T12","span":{"begin":56,"end":64},"obj":"P63131"},{"id":"T13","span":{"begin":56,"end":64},"obj":"Q9IIH4"},{"id":"T14","span":{"begin":56,"end":64},"obj":"P10270"},{"id":"T15","span":{"begin":56,"end":64},"obj":"Q8JN66"},{"id":"T16","span":{"begin":56,"end":64},"obj":"O40958"},{"id":"T17","span":{"begin":56,"end":64},"obj":"P10265"},{"id":"T18","span":{"begin":56,"end":64},"obj":"Q9QM72"},{"id":"T19","span":{"begin":56,"end":64},"obj":"P63119"},{"id":"T20","span":{"begin":56,"end":64},"obj":"Q9WF19"},{"id":"T21","span":{"begin":56,"end":64},"obj":"P63120"},{"id":"T22","span":{"begin":56,"end":64},"obj":"P63125"},{"id":"T23","span":{"begin":56,"end":64},"obj":"P63124"},{"id":"T24","span":{"begin":56,"end":64},"obj":"P68986"},{"id":"T25","span":{"begin":56,"end":64},"obj":"Q96629"},{"id":"T26","span":{"begin":56,"end":64},"obj":"P63121"},{"id":"T27","span":{"begin":56,"end":64},"obj":"P09569"},{"id":"T28","span":{"begin":56,"end":64},"obj":"P03253"},{"id":"T29","span":{"begin":56,"end":64},"obj":"P63129"},{"id":"T30","span":{"begin":56,"end":64},"obj":"P10381"},{"id":"T31","span":{"begin":56,"end":64},"obj":"P07885"},{"id":"T32","span":{"begin":56,"end":64},"obj":"Q83906"},{"id":"T33","span":{"begin":56,"end":64},"obj":"P19119"},{"id":"T34","span":{"begin":56,"end":64},"obj":"P63127"},{"id":"T35","span":{"begin":56,"end":64},"obj":"Q84177"},{"id":"T36","span":{"begin":56,"end":64},"obj":"P19151"},{"id":"T37","span":{"begin":56,"end":64},"obj":"Q9Y6I0"},{"id":"T38","span":{"begin":56,"end":64},"obj":"P63123"},{"id":"T39","span":{"begin":56,"end":64},"obj":"P68984"},{"id":"T40","span":{"begin":56,"end":64},"obj":"P87563"},{"id":"T41","span":{"begin":56,"end":64},"obj":"P03252"},{"id":"T42","span":{"begin":56,"end":64},"obj":"O71150"},{"id":"T43","span":{"begin":56,"end":64},"obj":"P11825"},{"id":"T44","span":{"begin":70,"end":101},"obj":"28295"},{"id":"T45","span":{"begin":70,"end":101},"obj":"D053485"},{"id":"T46","span":{"begin":87,"end":95},"obj":"D003967"},{"id":"T47","span":{"begin":87,"end":95},"obj":"D003967"},{"id":"T49","span":{"begin":120,"end":128},"obj":"D003967"},{"id":"T50","span":{"begin":120,"end":128},"obj":"D003967"},{"id":"T51","span":{"begin":136,"end":140},"obj":"28295"},{"id":"T52","span":{"begin":167,"end":171},"obj":"PR:Q9W3Y4"},{"id":"T55","span":{"begin":167,"end":171},"obj":"PR:Q6PD26"},{"id":"T56","span":{"begin":167,"end":171},"obj":"PR:Q5XI31"},{"id":"T57","span":{"begin":167,"end":171},"obj":"PR:Q96S52"},{"id":"T58","span":{"begin":167,"end":171},"obj":"PR:000012706"},{"id":"T53","span":{"begin":167,"end":171},"obj":"D013552"},{"id":"T54","span":{"begin":167,"end":171},"obj":"9823"},{"id":"T59","span":{"begin":173,"end":177},"obj":"28295"},{"id":"T99","span":{"begin":183,"end":194},"obj":"Q92876"},{"id":"T100","span":{"begin":183,"end":194},"obj":"PR:000009416"},{"id":"T105","span":{"begin":195,"end":198},"obj":"SO:0001439"},{"id":"T101","span":{"begin":195,"end":198},"obj":"CVCL_N817"},{"id":"T102","span":{"begin":195,"end":198},"obj":"CHEBI:32871"},{"id":"T103","span":{"begin":195,"end":198},"obj":"CHEBI:32865"},{"id":"T104","span":{"begin":195,"end":198},"obj":"CHEBI:50342"},{"id":"T106","span":{"begin":195,"end":198},"obj":"CHEBI:32866"},{"id":"T107","span":{"begin":228,"end":245},"obj":"GO:0019058"},{"id":"T108","span":{"begin":228,"end":245},"obj":"GO:0019079"},{"id":"T109","span":{"begin":228,"end":245},"obj":"GO:0008166"},{"id":"T110","span":{"begin":274,"end":278},"obj":"28295"},{"id":"T115","span":{"begin":281,"end":284},"obj":"SO:0001439"},{"id":"T112","span":{"begin":281,"end":284},"obj":"CHEBI:32871"},{"id":"T113","span":{"begin":281,"end":284},"obj":"CHEBI:32865"},{"id":"T114","span":{"begin":281,"end":284},"obj":"CHEBI:50342"},{"id":"T116","span":{"begin":281,"end":284},"obj":"CHEBI:32866"},{"id":"T111","span":{"begin":281,"end":284},"obj":"CVCL_N817"},{"id":"T117","span":{"begin":301,"end":315},"obj":"CHEBI:63175"},{"id":"T119","span":{"begin":316,"end":328},"obj":"CHEBI:39900"},{"id":"T120","span":{"begin":348,"end":356},"obj":"SO:0000164"},{"id":"T121","span":{"begin":348,"end":356},"obj":"CHEBI:15339"},{"id":"T122","span":{"begin":438,"end":448},"obj":"CHEBI:35222"},{"id":"T123","span":{"begin":475,"end":485},"obj":"CHEBI:35222"},{"id":"T124","span":{"begin":493,"end":496},"obj":"PR:000007889"},{"id":"T126","span":{"begin":493,"end":496},"obj":"PR:Q9S7S3"},{"id":"T128","span":{"begin":493,"end":496},"obj":"PR:Q6RFH4"},{"id":"T127","span":{"begin":493,"end":496},"obj":"CVCL_D028"},{"id":"T125","span":{"begin":493,"end":496},"obj":"CHEBI:140154"},{"id":"T129","span":{"begin":539,"end":543},"obj":"28295"},{"id":"T130","span":{"begin":546,"end":549},"obj":"CVCL_N817"},{"id":"T134","span":{"begin":546,"end":549},"obj":"SO:0001439"},{"id":"T131","span":{"begin":546,"end":549},"obj":"CHEBI:32871"},{"id":"T132","span":{"begin":546,"end":549},"obj":"CHEBI:32865"},{"id":"T133","span":{"begin":546,"end":549},"obj":"CHEBI:50342"},{"id":"T135","span":{"begin":546,"end":549},"obj":"CHEBI:32866"},{"id":"T136","span":{"begin":616,"end":620},"obj":"28295"},{"id":"T137","span":{"begin":621,"end":630},"obj":"D007239"},{"id":"T138","span":{"begin":621,"end":630},"obj":"D007239"}],"attributes":[{"subj":"T2","pred":"source","obj":"GoldHamster"},{"subj":"T1","pred":"source","obj":"GoldHamster"},{"subj":"T3","pred":"source","obj":"GoldHamster"},{"subj":"T4","pred":"source","obj":"GoldHamster"},{"subj":"T5","pred":"source","obj":"GoldHamster"},{"subj":"T6","pred":"source","obj":"GoldHamster"},{"subj":"T7","pred":"source","obj":"GoldHamster"},{"subj":"T8","pred":"source","obj":"GoldHamster"},{"subj":"T9","pred":"source","obj":"GoldHamster"},{"subj":"T10","pred":"source","obj":"GoldHamster"},{"subj":"T11","pred":"source","obj":"GoldHamster"},{"subj":"T12","pred":"source","obj":"GoldHamster"},{"subj":"T13","pred":"source","obj":"GoldHamster"},{"subj":"T14","pred":"source","obj":"GoldHamster"},{"subj":"T15","pred":"source","obj":"GoldHamster"},{"subj":"T16","pred":"source","obj":"GoldHamster"},{"subj":"T17","pred":"source","obj":"GoldHamster"},{"subj":"T18","pred":"source","obj":"GoldHamster"},{"subj":"T19","pred":"source","obj":"GoldHamster"},{"subj":"T20","pred":"source","obj":"GoldHamster"},{"subj":"T21","pred":"source","obj":"GoldHamster"},{"subj":"T22","pred":"source","obj":"GoldHamster"},{"subj":"T23","pred":"source","obj":"GoldHamster"},{"subj":"T24","pred":"source","obj":"GoldHamster"},{"subj":"T25","pred":"source","obj":"GoldHamster"},{"subj":"T26","pred":"source","obj":"GoldHamster"},{"subj":"T27","pred":"source","obj":"GoldHamster"},{"subj":"T28","pred":"source","obj":"GoldHamster"},{"subj":"T29","pred":"source","obj":"GoldHamster"},{"subj":"T30","pred":"source","obj":"GoldHamster"},{"subj":"T31","pred":"source","obj":"GoldHamster"},{"subj":"T32","pred":"source","obj":"GoldHamster"},{"subj":"T33","pred":"source","obj":"GoldHamster"},{"subj":"T34","pred":"source","obj":"GoldHamster"},{"subj":"T35","pred":"source","obj":"GoldHamster"},{"subj":"T36","pred":"source","obj":"GoldHamster"},{"subj":"T37","pred":"source","obj":"GoldHamster"},{"subj":"T38","pred":"source","obj":"GoldHamster"},{"subj":"T39","pred":"source","obj":"GoldHamster"},{"subj":"T40","pred":"source","obj":"GoldHamster"},{"subj":"T41","pred":"source","obj":"GoldHamster"},{"subj":"T42","pred":"source","obj":"GoldHamster"},{"subj":"T43","pred":"source","obj":"GoldHamster"},{"subj":"T44","pred":"source","obj":"GoldHamster"},{"subj":"T45","pred":"source","obj":"GoldHamster"},{"subj":"T46","pred":"source","obj":"GoldHamster"},{"subj":"T47","pred":"source","obj":"GoldHamster"},{"subj":"T49","pred":"source","obj":"GoldHamster"},{"subj":"T50","pred":"source","obj":"GoldHamster"},{"subj":"T51","pred":"source","obj":"GoldHamster"},{"subj":"T52","pred":"source","obj":"GoldHamster"},{"subj":"T55","pred":"source","obj":"GoldHamster"},{"subj":"T56","pred":"source","obj":"GoldHamster"},{"subj":"T57","pred":"source","obj":"GoldHamster"},{"subj":"T58","pred":"source","obj":"GoldHamster"},{"subj":"T53","pred":"source","obj":"GoldHamster"},{"subj":"T54","pred":"source","obj":"GoldHamster"},{"subj":"T59","pred":"source","obj":"GoldHamster"},{"subj":"T99","pred":"source","obj":"GoldHamster"},{"subj":"T100","pred":"source","obj":"GoldHamster"},{"subj":"T105","pred":"source","obj":"GoldHamster"},{"subj":"T101","pred":"source","obj":"GoldHamster"},{"subj":"T102","pred":"source","obj":"GoldHamster"},{"subj":"T103","pred":"source","obj":"GoldHamster"},{"subj":"T104","pred":"source","obj":"GoldHamster"},{"subj":"T106","pred":"source","obj":"GoldHamster"},{"subj":"T107","pred":"source","obj":"GoldHamster"},{"subj":"T108","pred":"source","obj":"GoldHamster"},{"subj":"T109","pred":"source","obj":"GoldHamster"},{"subj":"T110","pred":"source","obj":"GoldHamster"},{"subj":"T115","pred":"source","obj":"GoldHamster"},{"subj":"T112","pred":"source","obj":"GoldHamster"},{"subj":"T113","pred":"source","obj":"GoldHamster"},{"subj":"T114","pred":"source","obj":"GoldHamster"},{"subj":"T116","pred":"source","obj":"GoldHamster"},{"subj":"T111","pred":"source","obj":"GoldHamster"},{"subj":"T117","pred":"source","obj":"GoldHamster"},{"subj":"T119","pred":"source","obj":"GoldHamster"},{"subj":"T120","pred":"source","obj":"GoldHamster"},{"subj":"T121","pred":"source","obj":"GoldHamster"},{"subj":"T122","pred":"source","obj":"GoldHamster"},{"subj":"T123","pred":"source","obj":"GoldHamster"},{"subj":"T124","pred":"source","obj":"GoldHamster"},{"subj":"T126","pred":"source","obj":"GoldHamster"},{"subj":"T128","pred":"source","obj":"GoldHamster"},{"subj":"T127","pred":"source","obj":"GoldHamster"},{"subj":"T125","pred":"source","obj":"GoldHamster"},{"subj":"T129","pred":"source","obj":"GoldHamster"},{"subj":"T130","pred":"source","obj":"GoldHamster"},{"subj":"T134","pred":"source","obj":"GoldHamster"},{"subj":"T131","pred":"source","obj":"GoldHamster"},{"subj":"T132","pred":"source","obj":"GoldHamster"},{"subj":"T133","pred":"source","obj":"GoldHamster"},{"subj":"T135","pred":"source","obj":"GoldHamster"},{"subj":"T136","pred":"source","obj":"GoldHamster"},{"subj":"T137","pred":"source","obj":"GoldHamster"},{"subj":"T138","pred":"source","obj":"GoldHamster"}]},{"project":"Goldhamster2_Cellosaurus","denotations":[{"id":"T1","span":{"begin":193,"end":199},"obj":"CVCL_5430|Spontaneously_immortalized_cell_line|Mus musculus"},{"id":"T2","span":{"begin":195,"end":198},"obj":"CVCL_N817|Cancer_cell_line|Homo sapiens"},{"id":"T3","span":{"begin":207,"end":209},"obj":"CVCL_8754|Cancer_cell_line|Homo sapiens"},{"id":"T4","span":{"begin":207,"end":209},"obj":"CVCL_H241|Cancer_cell_line|Homo sapiens"},{"id":"T5","span":{"begin":234,"end":245},"obj":"CVCL_XY58|Transformed_cell_line|Mus musculus"},{"id":"T6","span":{"begin":247,"end":249},"obj":"CVCL_5M23|Cancer_cell_line|Mesocricetus auratus"},{"id":"T7","span":{"begin":279,"end":285},"obj":"CVCL_5430|Spontaneously_immortalized_cell_line|Mus musculus"},{"id":"T8","span":{"begin":281,"end":284},"obj":"CVCL_N817|Cancer_cell_line|Homo sapiens"},{"id":"T9","span":{"begin":326,"end":328},"obj":"CVCL_D435|Transformed_cell_line|Mus musculus"},{"id":"T10","span":{"begin":326,"end":328},"obj":"CVCL_ZU49|Transformed_cell_line|Homo sapiens"},{"id":"T11","span":{"begin":338,"end":339},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T12","span":{"begin":403,"end":405},"obj":"CVCL_5M23|Cancer_cell_line|Mesocricetus auratus"},{"id":"T13","span":{"begin":423,"end":424},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T14","span":{"begin":486,"end":488},"obj":"CVCL_M543|Cancer_cell_line|Homo sapiens"},{"id":"T15","span":{"begin":486,"end":488},"obj":"CVCL_W291|Cancer_cell_line|Homo sapiens"},{"id":"T16","span":{"begin":486,"end":488},"obj":"CVCL_XD77|Embryonic_stem_cell|Homo sapiens"},{"id":"T17","span":{"begin":493,"end":496},"obj":"CVCL_D028|Cancer_cell_line|Homo sapiens"},{"id":"T18","span":{"begin":544,"end":550},"obj":"CVCL_5430|Spontaneously_immortalized_cell_line|Mus musculus"},{"id":"T19","span":{"begin":546,"end":549},"obj":"CVCL_N817|Cancer_cell_line|Homo sapiens"}],"attributes":[{"subj":"T1","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T2","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T3","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T4","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T5","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T6","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T7","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T8","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T9","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T10","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T11","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T12","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T13","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T14","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T15","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T16","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T17","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T18","pred":"source","obj":"Goldhamster2_Cellosaurus"},{"subj":"T19","pred":"source","obj":"Goldhamster2_Cellosaurus"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubMed_ArguminSci","color":"#93ceec","default":true},{"id":"GoldHamster","color":"#e8ec93"},{"id":"Goldhamster2_Cellosaurus","color":"#d593ec"}]}]}}