{"id":"https://openalex.org/W3009264613","doi":"https://doi.org/10.1021/acs.jcim.9b01138","title":"Assessment of the Cruzain Cysteine Protease Reversible and Irreversible Covalent Inhibition Mechanism","display_name":"Assessment of the Cruzain Cysteine Protease Reversible and Irreversible Covalent Inhibition Mechanism","publication_year":2020,"publication_date":"2020-03-03","ids":{"openalex":"https://openalex.org/W3009264613","doi":"https://doi.org/10.1021/acs.jcim.9b01138","mag":"3009264613","pmid":"https://pubmed.ncbi.nlm.nih.gov/32126170"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.9b01138","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.9b01138","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5053248481","display_name":"Jos\u00e9 Rog\u00e9rio A. Silva","orcid":"https://orcid.org/0000-0003-2310-5107"},"institutions":[{"id":"https://openalex.org/I59606676","display_name":"Universidade Federal do Par\u00e1","ror":"https://ror.org/03q9sr818","country_code":"BR","type":"education","lineage":["https://openalex.org/I59606676"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Jos\u00e9 Rog\u00e9rio A. Silva","raw_affiliation_strings":["Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos. Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Rua Augusto Corr\u00eaa 01, CEP 66075-110, Bel\u00e9m, Par\u00e1, Brazil"],"raw_orcid":"https://orcid.org/0000-0003-2310-5107","affiliations":[{"raw_affiliation_string":"Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos. Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Rua Augusto Corr\u00eaa 01, CEP 66075-110, Bel\u00e9m, Par\u00e1, Brazil","institution_ids":["https://openalex.org/I59606676"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002516080","display_name":"Lorenzo Cianni","orcid":"https://orcid.org/0000-0002-3668-9554"},"institutions":[{"id":"https://openalex.org/I17974374","display_name":"Universidade de S\u00e3o Paulo","ror":"https://ror.org/036rp1748","country_code":"BR","type":"education","lineage":["https://openalex.org/I17974374"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Lorenzo Cianni","raw_affiliation_strings":["Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil","institution_ids":["https://openalex.org/I17974374"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000056732","display_name":"Deborah Araujo","orcid":"https://orcid.org/0000-0002-9218-3566"},"institutions":[{"id":"https://openalex.org/I17974374","display_name":"Universidade de S\u00e3o Paulo","ror":"https://ror.org/036rp1748","country_code":"BR","type":"education","lineage":["https://openalex.org/I17974374"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Deborah Araujo","raw_affiliation_strings":["Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil","institution_ids":["https://openalex.org/I17974374"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020271117","display_name":"Pedro Henrique Jata\u00ed Batista","orcid":"https://orcid.org/0000-0002-7185-4981"},"institutions":[{"id":"https://openalex.org/I17974374","display_name":"Universidade de S\u00e3o Paulo","ror":"https://ror.org/036rp1748","country_code":"BR","type":"education","lineage":["https://openalex.org/I17974374"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Pedro Henrique Jatai Batista","raw_affiliation_strings":["Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil","institution_ids":["https://openalex.org/I17974374"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073685383","display_name":"Daniela De Vita","orcid":"https://orcid.org/0000-0002-0370-4244"},"institutions":[{"id":"https://openalex.org/I17974374","display_name":"Universidade de S\u00e3o Paulo","ror":"https://ror.org/036rp1748","country_code":"BR","type":"education","lineage":["https://openalex.org/I17974374"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Daniela de Vita","raw_affiliation_strings":["Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil","institution_ids":["https://openalex.org/I17974374"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066874620","display_name":"Fabiana Rosini","orcid":null},"institutions":[{"id":"https://openalex.org/I17974374","display_name":"Universidade de S\u00e3o Paulo","ror":"https://ror.org/036rp1748","country_code":"BR","type":"education","lineage":["https://openalex.org/I17974374"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Fabiana Rosini","raw_affiliation_strings":["Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil","institution_ids":["https://openalex.org/I17974374"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040801454","display_name":"Andrei Leit\u00e3o","orcid":"https://orcid.org/0000-0002-6601-6609"},"institutions":[{"id":"https://openalex.org/I17974374","display_name":"Universidade de S\u00e3o Paulo","ror":"https://ror.org/036rp1748","country_code":"BR","type":"education","lineage":["https://openalex.org/I17974374"]}],"countries":["BR"],"is_corresponding":false,"raw_author_name":"Andrei Leit\u00e3o","raw_affiliation_strings":["Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil","institution_ids":["https://openalex.org/I17974374"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5087137334","display_name":"Jer\u00f4nimo Lameira","orcid":"https://orcid.org/0000-0001-7270-1517"},"institutions":[{"id":"https://openalex.org/I59606676","display_name":"Universidade Federal do Par\u00e1","ror":"https://ror.org/03q9sr818","country_code":"BR","type":"education","lineage":["https://openalex.org/I59606676"]}],"countries":["BR"],"is_corresponding":true,"raw_author_name":"Jer\u00f4nimo Lameira","raw_affiliation_strings":["Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos. Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Rua Augusto Corr\u00eaa 01, CEP 66075-110, Bel\u00e9m, Par\u00e1, Brazil"],"raw_orcid":"https://orcid.org/0000-0001-7270-1517","affiliations":[{"raw_affiliation_string":"Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos. Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Rua Augusto Corr\u00eaa 01, CEP 66075-110, Bel\u00e9m, Par\u00e1, Brazil","institution_ids":["https://openalex.org/I59606676"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5039642161","display_name":"Carlos A. Montanari","orcid":"https://orcid.org/0000-0002-4963-0316"},"institutions":[{"id":"https://openalex.org/I17974374","display_name":"Universidade de S\u00e3o Paulo","ror":"https://ror.org/036rp1748","country_code":"BR","type":"education","lineage":["https://openalex.org/I17974374"]}],"countries":["BR"],"is_corresponding":true,"raw_author_name":"Carlos A. Montanari","raw_affiliation_strings":["Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil"],"raw_orcid":"https://orcid.org/0000-0002-4963-0316","affiliations":[{"raw_affiliation_string":"Medicinal Chemistry Group, Institute of Chemistry of S\u00e3o Carlos, University of S\u00e3o Paulo, Avenue Trabalhador Sancarlense 400, 23566-590, S\u00e3o Carlos, S\u00e3o Paulo, Brazil","institution_ids":["https://openalex.org/I17974374"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5039642161","https://openalex.org/A5087137334"],"corresponding_institution_ids":["https://openalex.org/I17974374","https://openalex.org/I59606676"],"apc_list":null,"apc_paid":null,"fwci":3.1517,"has_fulltext":false,"cited_by_count":45,"citation_normalized_percentile":{"value":0.92765895,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":96,"max":99},"biblio":{"volume":"60","issue":"3","first_page":"1666","last_page":"1677"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11440","display_name":"Click Chemistry and Applications","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11440","display_name":"Click Chemistry and Applications","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.9907000064849854,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12505","display_name":"Peptidase Inhibition and Analysis","score":0.9822999835014343,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/cysteine","display_name":"Cysteine","score":0.7555375099182129},{"id":"https://openalex.org/keywords/cysteine-protease","display_name":"Cysteine protease","score":0.7356585264205933},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.6620402336120605},{"id":"https://openalex.org/keywords/mechanism","display_name":"Mechanism (biology)","score":0.6208690404891968},{"id":"https://openalex.org/keywords/covalent-bond","display_name":"Covalent bond","score":0.5280271768569946},{"id":"https://openalex.org/keywords/protease","display_name":"Protease","score":0.5085619688034058},{"id":"https://openalex.org/keywords/cysteine-proteinase-inhibitors","display_name":"Cysteine Proteinase Inhibitors","score":0.45982909202575684},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.44821563363075256},{"id":"https://openalex.org/keywords/protease-inhibitor","display_name":"Protease inhibitor (pharmacology)","score":0.42893218994140625},{"id":"https://openalex.org/keywords/pharmacology","display_name":"Pharmacology","score":0.3342564105987549},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.31679701805114746},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.16836553812026978},{"id":"https://openalex.org/keywords/organic-chemistry","display_name":"Organic chemistry","score":0.09925007820129395},{"id":"https://openalex.org/keywords/virology","display_name":"Virology","score":0.07546976208686829}],"concepts":[{"id":"https://openalex.org/C2779201268","wikidata":"https://www.wikidata.org/wiki/Q186474","display_name":"Cysteine","level":3,"score":0.7555375099182129},{"id":"https://openalex.org/C2777283782","wikidata":"https://www.wikidata.org/wiki/Q419343","display_name":"Cysteine protease","level":4,"score":0.7356585264205933},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6620402336120605},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.6208690404891968},{"id":"https://openalex.org/C180577832","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent bond","level":2,"score":0.5280271768569946},{"id":"https://openalex.org/C2776714187","wikidata":"https://www.wikidata.org/wiki/Q212410","display_name":"Protease","level":3,"score":0.5085619688034058},{"id":"https://openalex.org/C2908725733","wikidata":"https://www.wikidata.org/wiki/Q419343","display_name":"Cysteine Proteinase Inhibitors","level":5,"score":0.45982909202575684},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.44821563363075256},{"id":"https://openalex.org/C2781143361","wikidata":"https://www.wikidata.org/wiki/Q55761529","display_name":"Protease inhibitor (pharmacology)","level":5,"score":0.42893218994140625},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3342564105987549},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.31679701805114746},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.16836553812026978},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.09925007820129395},{"id":"https://openalex.org/C159047783","wikidata":"https://www.wikidata.org/wiki/Q7215","display_name":"Virology","level":1,"score":0.07546976208686829},{"id":"https://openalex.org/C142462285","wikidata":"https://www.wikidata.org/wiki/Q2528140","display_name":"Viral load","level":3,"score":0.0},{"id":"https://openalex.org/C138885662","wikidata":"https://www.wikidata.org/wiki/Q5891","display_name":"Philosophy","level":0,"score":0.0},{"id":"https://openalex.org/C3013748606","wikidata":"https://www.wikidata.org/wiki/Q15787","display_name":"Human immunodeficiency virus (HIV)","level":2,"score":0.0},{"id":"https://openalex.org/C111472728","wikidata":"https://www.wikidata.org/wiki/Q9471","display_name":"Epistemology","level":1,"score":0.0},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.0},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.0},{"id":"https://openalex.org/C98424977","wikidata":"https://www.wikidata.org/wiki/Q25805","display_name":"Caspase","level":4,"score":0.0},{"id":"https://openalex.org/C2993143319","wikidata":"https://www.wikidata.org/wiki/Q583050","display_name":"Antiretroviral therapy","level":4,"score":0.0}],"mesh":[{"descriptor_ui":"D003546","descriptor_name":"Cysteine Endopeptidases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003546","descriptor_name":"Cysteine Endopeptidases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003546","descriptor_name":"Cysteine Endopeptidases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014349","descriptor_name":"Trypanosoma cruzi","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D014349","descriptor_name":"Trypanosoma cruzi","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D014349","descriptor_name":"Trypanosoma cruzi","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015800","descriptor_name":"Protozoan Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015800","descriptor_name":"Protozoan Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015800","descriptor_name":"Protozoan Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015853","descriptor_name":"Cysteine Proteinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D015853","descriptor_name":"Cysteine Proteinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D015853","descriptor_name":"Cysteine Proteinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D057056","descriptor_name":"Cysteine Proteases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D057056","descriptor_name":"Cysteine Proteases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D057056","descriptor_name":"Cysteine Proteases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1021/acs.jcim.9b01138","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.9b01138","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:32126170","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/32126170","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of chemical information and modeling","raw_type":null},{"id":"pmh:oai:iris.uniroma1.it:11573/1404853","is_oa":false,"landing_page_url":"http://hdl.handle.net/11573/1404853","pdf_url":null,"source":{"id":"https://openalex.org/S4377196107","display_name":"IRIS Research product catalog (Sapienza University of Rome)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"info:eu-repo/semantics/article"}],"best_oa_location":null,"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G4867179095","display_name":"Computational study of cruzain enzyme by reversible covalent inhibitors","funder_award_id":"18/21749-3","funder_id":"https://openalex.org/F4320320997","funder_display_name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo"},{"id":"https://openalex.org/G7965448828","display_name":null,"funder_award_id":"407096/2016-7","funder_id":"https://openalex.org/F4320322025","funder_display_name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico"},{"id":"https://openalex.org/G8890151708","display_name":"Molecular design, synthesis and trypanocidal activity of cruzain reversible covalent inhibitors","funder_award_id":"13/18009-4","funder_id":"https://openalex.org/F4320320997","funder_display_name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo"}],"funders":[{"id":"https://openalex.org/F4320320997","display_name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","ror":"https://ror.org/02ddkpn78"},{"id":"https://openalex.org/F4320322025","display_name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","ror":"https://ror.org/03swz6y49"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":56,"referenced_works":["https://openalex.org/W1625910593","https://openalex.org/W1968166922","https://openalex.org/W1968451199","https://openalex.org/W1968994875","https://openalex.org/W1975430993","https://openalex.org/W1976499671","https://openalex.org/W1977334898","https://openalex.org/W1980525207","https://openalex.org/W1982604887","https://openalex.org/W1984075743","https://openalex.org/W2004303971","https://openalex.org/W2006727669","https://openalex.org/W2010654750","https://openalex.org/W2014189709","https://openalex.org/W2020642787","https://openalex.org/W2021981535","https://openalex.org/W2021996491","https://openalex.org/W2029079594","https://openalex.org/W2033938279","https://openalex.org/W2041541639","https://openalex.org/W2049102964","https://openalex.org/W2056403222","https://openalex.org/W2059737570","https://openalex.org/W2061532598","https://openalex.org/W2065861223","https://openalex.org/W2076888175","https://openalex.org/W2080780049","https://openalex.org/W2081771891","https://openalex.org/W2095258814","https://openalex.org/W2096864392","https://openalex.org/W2111066407","https://openalex.org/W2115802085","https://openalex.org/W2127073449","https://openalex.org/W2143287044","https://openalex.org/W2147993766","https://openalex.org/W2327581403","https://openalex.org/W2342445885","https://openalex.org/W2404280981","https://openalex.org/W2410141289","https://openalex.org/W2511955955","https://openalex.org/W2566502318","https://openalex.org/W2589958932","https://openalex.org/W2598528124","https://openalex.org/W2612329522","https://openalex.org/W2705421977","https://openalex.org/W2763673935","https://openalex.org/W2779060209","https://openalex.org/W2785841326","https://openalex.org/W2802832877","https://openalex.org/W2889785065","https://openalex.org/W2911268412","https://openalex.org/W2913105929","https://openalex.org/W2914871918","https://openalex.org/W2964899800","https://openalex.org/W2981994760","https://openalex.org/W2987941122"],"related_works":["https://openalex.org/W2077515371","https://openalex.org/W2083934724","https://openalex.org/W2011205061","https://openalex.org/W2437509053","https://openalex.org/W2006984383","https://openalex.org/W2030198142","https://openalex.org/W2912727447","https://openalex.org/W1988598700","https://openalex.org/W4319460365","https://openalex.org/W2115123186"],"abstract_inverted_index":{"Reversible":[0],"and":[1,89,103,136,155,169,182,203,210,246],"irreversible":[2,18,46,104,119,187],"covalent":[3,47,76,188,237,261],"ligands":[4],"are":[5,49],"advanced":[6,87],"cysteine":[7,82,265],"protease":[8],"inhibitors":[9,48],"in":[10,174],"the":[11,26,29,37,55,63,96,145,148,165,197,213,221,225,231,236,254],"drug":[12],"development":[13],"pipeline.":[14],"K777":[15,64,154,209],"is":[16,121,227],"an":[17,118,186],"inhibitor":[19,77,120,181],"of":[20,28,40,57,81,95,99,115,147,151,224,264],"cruzain,":[21],"a":[22,69,74,127,175,179,242,260],"necessary":[23],"enzyme":[24],"for":[25,178,185,196,208,230],"survival":[27],"Trypanosoma":[30],"cruzi":[31,34],"(":[32,78],"T.":[33],")":[35,80],"parasite,":[36],"causative":[38],"agent":[39],"Chagas":[41],"disease.":[42],"Despite":[43],"their":[44],"importance,":[45],"still":[50],"often":[51],"avoided":[52],"due":[53],"to":[54,72,92,143,201,241,250],"risk":[56],"adverse":[58],"effects.":[59],"Herein,":[60],"we":[61,85],"replaced":[62],"vinyl":[65],"sulfone":[66],"group":[67],"with":[68],"nitrile":[70],"moiety":[71],"obtain":[73],"reversible":[75,102,128,180],"Neq0682":[79,156,211],"protease.":[83],"Then,":[84],"used":[86,142],"experimental":[88],"computational":[90],"techniques":[91],"explore":[93,144],"details":[94],"inhibition":[97,114,150,198,262],"mechanism":[98,146,263],"cruzain":[100,116,152],"by":[101,117,126,153],"inhibitors.":[105],"The":[106,130,158,190],"isothermal":[107],"titration":[108],"calorimetry":[109],"(ITC)":[110],"analysis":[111],"shows":[112],"that":[113,164,220],"thermodynamically":[122],"more":[123],"favorable":[124],"than":[125],"one.":[129],"hybrid":[131,191],"Quantum":[132],"Mechanics/Molecular":[133],"Mechanics":[134],"(QM/MM)":[135],"Molecular":[137],"Dynamics":[138],"(MD)":[139],"simulations":[140],"were":[141],"reaction":[149,199,226],".":[157],"calculated":[159,193],"free":[160,194],"energy":[161],"profiles":[162],"show":[163],"Cys25":[166],"nucleophilic":[167],"attack":[168],"His162":[170],"proton":[171],"transfer":[172],"occur":[173],"single":[176],"step":[177],"two":[183],"steps":[184],"inhibitor.":[189],"QM/MM":[192],"energies":[195],"correspond":[200],"\u221226.7":[202],"\u22125.9":[204],"kcal":[205],"mol":[206],"\u20131":[207],"at":[212],"MP2/MM":[214],"level,":[215],"respectively.":[216],"These":[217],"results":[218],"indicate":[219],"\u0394":[222],"G":[223],"very":[228],"negative":[229],"process":[232],"involving":[233],"K777,":[234],"consequently,":[235],"adduct":[238],"cannot":[239],"revert":[240],"noncovalent":[243],"protein\u2013ligand":[244],"complex,":[245],"its":[247],"binding":[248],"tends":[249],"be":[251],"irreversible.":[252],"Overall,":[253],"present":[255],"study":[256],"provides":[257],"insights":[258],"into":[259],"proteases.":[266]},"counts_by_year":[{"year":2026,"cited_by_count":4},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":5},{"year":2023,"cited_by_count":10},{"year":2022,"cited_by_count":7},{"year":2021,"cited_by_count":9},{"year":2020,"cited_by_count":7}],"updated_date":"2026-08-06T08:24:18.245995","created_date":"2025-10-10T00:00:00"}