{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:44:46Z","timestamp":1790189086770,"version":"4.1.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2023,9]]},"DOI":"10.1016\/j.ejmech.2023.115487","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:57:31Z","timestamp":1684889851000},"page":"115487","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"special_numbering":"C","title":["Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro)"],"prefix":"10.1016","volume":"257","author":[{"given":"Kuojun","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maotian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhua","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-4765","authenticated-orcid":false,"given":"Xiangyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2023.115487_bib1","unstructured":"WHO, WHO Coronavirus Disease (COVID-19) Dashboard. https:\/\/covid19.who.int\/(accessed date: 2022.December.14)."},{"key":"10.1016\/j.ejmech.2023.115487_bib2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/d41586-022-00562-0","article-title":"Hundreds of COVID trials could provide a deluge of new drugs","volume":"603","author":"Ledford","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2023.115487_bib3","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1021\/acscentsci.1c00120","article-title":"A comprehensive review of the global efforts on COVID-19 vaccine development","volume":"7","author":"Li","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"10.1016\/j.ejmech.2023.115487_bib4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41577-021-00662-4","article-title":"SARS-CoV-2 breakthrough infections in vaccinated individuals: measurement, causes and impact","volume":"22","author":"Lipsitch","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejmech.2023.115487_bib5","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/S0140-6736(22)00152-0","article-title":"Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression","volume":"399","author":"Feikin","year":"2022","journal-title":"Lancet (London, England)"},{"key":"10.1016\/j.ejmech.2023.115487_bib6","first-page":"1","article-title":"Omicron variant (B.1.1.529): infectivity, vaccine breakthrough, and antibody resistance","volume":"10","author":"Ren","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2023.115487_bib7","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41586-021-04387-1","article-title":"Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization","volume":"602","author":"Cele","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2023.115487_bib8","unstructured":"."},{"key":"10.1016\/j.ejmech.2023.115487_bib9","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1021\/acs.jmedchem.0c01140","article-title":"Targeting SARS-CoV-2 proteases and polymerase for COVID-19 treatment: state of the art and future opportunities","volume":"65","author":"Cannalire","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib10","doi-asserted-by":"crossref","first-page":"16922","DOI":"10.1021\/acs.jmedchem.1c00409","article-title":"Perspectives on SARS-CoV-2 main protease inhibitors","volume":"64","author":"Gao","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib11","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1021\/acs.jmedchem.2c00117","article-title":"Discovery of S-217622, a noncovalent oral SARS-CoV-2 3CL protease inhibitor clinical candidate for treating COVID-19","volume":"65","author":"Unoh","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib12","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1126\/science.abg5827","article-title":"Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2","volume":"373","author":"Drayman","year":"2021","journal-title":"Science (New York, N.Y.)"},{"key":"10.1016\/j.ejmech.2023.115487_bib13","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abl4784","article-title":"An oral SARS-CoV-2 M(pro) inhibitor clinical candidate for the treatment of COVID-19","volume":"374","author":"Owen","year":"2021","journal-title":"Science (New York, N.Y.)"},{"key":"10.1016\/j.ejmech.2023.115487_bib14","doi-asserted-by":"crossref","first-page":"12725","DOI":"10.1021\/acs.jmedchem.0c01063","article-title":"Discovery of Ketone-based bovalent inhibitors of coronavirus 3CL proteases for the potential therapeutic treatment of COVID-19","volume":"63","author":"Hoffman","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib15","doi-asserted-by":"crossref","first-page":"6055","DOI":"10.1038\/s41467-021-26239-2","article-title":"Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19","volume":"12","author":"Boras","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2023.115487_bib16","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41422-020-0356-z","article-title":"376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease","volume":"30","author":"Ma","year":"2020","journal-title":"Cell Res."},{"key":"10.1016\/j.ejmech.2023.115487_bib17","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1126\/science.abf1611","article-title":"SARS-CoV-2 M(pro) inhibitors with antiviral activity in a transgenic mouse model","volume":"371","author":"Qiao","year":"2021","journal-title":"Science (New York, N.Y.)"},{"key":"10.1016\/j.ejmech.2023.115487_bib18","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1126\/science.abb4489","article-title":"Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease","volume":"368","author":"Dai","year":"2020","journal-title":"Science (New York, N.Y.)"},{"key":"10.1016\/j.ejmech.2023.115487_bib19","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","article-title":"Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved \u03b1-ketoamide inhibitors","volume":"368","author":"Zhang","year":"2020","journal-title":"Science (New York, N.Y.)"},{"key":"10.1016\/j.ejmech.2023.115487_bib20","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1021\/acs.jmedchem.1c00598","article-title":"Structure-based optimization of ML300-derived, noncovalent inhibitors targeting the severe acute respiratory syndrome coronavirus 3CL protease (SARS-CoV-2 3CL(pro))","volume":"65","author":"Han","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib21","doi-asserted-by":"crossref","first-page":"17366","DOI":"10.1021\/acs.jmedchem.1c01475","article-title":"Structural, electronic, and electrostatic determinants for inhibitor binding to subsites S1 and S2 in SARS-CoV-2 main protease","volume":"64","author":"Kneller","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib22","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/s41401-020-0483-6","article-title":"Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients","volume":"41","author":"Su","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.ejmech.2023.115487_bib23","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1021\/acs.jmedchem.1c00509","article-title":"Expedited approach toward the rational design of noncovalent SARS-CoV-2 main protease inhibitors","volume":"65","author":"Kitamura","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib24","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1021\/jacs.1c08402","article-title":"Ultralarge virtual screening identifies SARS-CoV-2 main protease inhibitors with broad-spectrum activity against coronaviruses","volume":"144","author":"Luttens","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2023.115487_bib25","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1021\/acscentsci.1c00039","article-title":"Potent noncovalent inhibitors of the main protease of SARS-CoV-2 from molecular sculpting of the drug perampanel guided by free energy perturbation calculations","volume":"7","author":"Zhang","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"10.1016\/j.ejmech.2023.115487_bib26","doi-asserted-by":"crossref","DOI":"10.1128\/aac.00697-22","article-title":"A randomized phase 2\/3 study of Ensitrelvir, a novel oral SARS-CoV-2 3C-Like protease inhibitor, in Japanese patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection: results of the phase 2a part","volume":"66","author":"Mukae","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115487_bib27","doi-asserted-by":"crossref","first-page":"7968","DOI":"10.1021\/jo701384n","article-title":"Sequential Cu-catalyzed amidation-base-mediated camps cyclization: a two-step synthesis of 2-aryl-4-quinolones from o-halophenones","volume":"72","author":"Jones","year":"2007","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib28","doi-asserted-by":"crossref","first-page":"4964","DOI":"10.1021\/jm049876x","article-title":"Antimitotic activity of 5-hydroxy-7-methoxy-2-phenyl-4-quinolones","volume":"47","author":"Hadjeri","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib29","doi-asserted-by":"crossref","first-page":"18815","DOI":"10.1021\/ja411146x","article-title":"Polycationic ligands in gold catalysis: synthesis and applications of extremely \u03c0-acidic catalysts","volume":"135","author":"Carreras","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2023.115487_bib30","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/anie.200804675","article-title":"A simple and efficient approach to quinazolinones under mild copper-catalyzed conditions","volume":"48","author":"Liu","year":"2009","journal-title":"Angew. Chem., Int. Ed. Engl."},{"key":"10.1016\/j.ejmech.2023.115487_bib31","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.ejmech.2013.05.043","article-title":"Synthesis and anticancer activities of 5,6,7-trimethoxy-N-phenyl(ethyl)-4-aminoquinazoline derivatives","volume":"66","author":"Zhang","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib32","doi-asserted-by":"crossref","first-page":"62194","DOI":"10.1039\/C5RA11262A","article-title":"Metal-free one-pot synthesis of 1,3-diazaheterocyclic compounds via I2-mediated oxidative C\u2013N bond formation","volume":"5","author":"Tian","year":"2015","journal-title":"RSC Adv."},{"key":"10.1016\/j.ejmech.2023.115487_bib33","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1021\/jo049118e","article-title":"A facile synthesis of C2,N3-disubstituted-4-quinazolone","volume":"69","author":"Xue","year":"2004","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib34","doi-asserted-by":"crossref","first-page":"8951","DOI":"10.1021\/acs.jmedchem.1c00004","article-title":"Discovery, optimization, and evaluation of quinazolinone derivatives with novel linkers as orally efficacious phosphoinositide-3-kinase delta inhibitors for treatment of inflammatory diseases","volume":"64","author":"Liu","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib35","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1021\/jm5019093","article-title":"PAINS in the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS","volume":"58","author":"Dahlin","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib36","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/s41564-022-01119-7","article-title":"An orally available M(pro) inhibitor is effective against wild-type SARS-CoV-2 and variants including Omicron","volume":"7","author":"Quan","year":"2022","journal-title":"Nat. Microbiol."},{"key":"10.1016\/j.ejmech.2023.115487_bib37","doi-asserted-by":"crossref","first-page":"16252","DOI":"10.1021\/acs.jmedchem.2c00954","article-title":"Structure-based design of a dual-targeted covalent inhibitor against papain-like and main proteases of SARS-CoV-2","volume":"65","author":"Yu","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2021.116523","article-title":"Synthesis and evaluation of enantiomers of hydroxychloroquine against SARS-CoV-2 in vitro","volume":"53","author":"Ni","year":"2022","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115487_bib39","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1107\/S0021889807021206","article-title":"Phaser crystallographic software","volume":"40","author":"McCoy","year":"2007","journal-title":"J. Appl. Crystallogr."},{"key":"10.1016\/j.ejmech.2023.115487_bib40","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2023.115487_bib41","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1107\/S0907444909029436","article-title":"Electronic ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation","volume":"65","author":"Moriarty","year":"2009","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2023.115487_bib42","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1107\/S0907444912001308","article-title":"Towards automated crystallographic structure refinement with phenix","volume":"68","author":"Afonine","year":"2012","journal-title":"refine. Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2023.115487_bib43","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2023.115487_bib44","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: more and better reference data for improved all-atom structure validation","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423004531?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423004531?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T14:51:48Z","timestamp":1730991108000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523423004531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":44,"alternative-id":["S0223523423004531"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115487","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro)","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115487","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115487"}}