{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T03:11:24Z","timestamp":1787454684521,"version":"build-2736575974"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1004304"],"award-info":[{"award-number":["2022YFA1004304"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009252","name":"Science for Life Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009252","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22277129"],"award-info":[{"award-number":["22277129"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273897"],"award-info":[{"award-number":["82273897"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Chemico-Biological Interactions"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.cbi.2025.111620","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T02:38:39Z","timestamp":1750732719000},"page":"111620","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Thiazole-fused thiazoliniums with ketone warheads as covalent inhibitors targeting Cys44 of SARS-CoV-2 3CLpro"],"prefix":"10.1016","volume":"418","author":[{"given":"Qizhen","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanfeng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinben","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3063-8473","authenticated-orcid":false,"given":"Zhijian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruisheng","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiliang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangbo","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4279-4596","authenticated-orcid":false,"given":"Bo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cbi.2025.111620_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.sbi.2023.102667","article-title":"Structural biology of SARS-CoV-2 Mpro and drug discovery","volume":"82","author":"Duan","year":"2023","journal-title":"J. Curr. Opin. Struct. Biol."},{"issue":"11","key":"10.1016\/j.cbi.2025.111620_bib2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41579-021-00630-8","article-title":"Structural biology of SARS-CoV-2 and implications for therapeutic development","volume":"19","author":"Yang","year":"2021","journal-title":"J. Nat. Rev. Microbiol."},{"issue":"Pt 3","key":"10.1016\/j.cbi.2025.111620_bib3","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1099\/0022-1317-83-3-595","article-title":"Conservation of substrate specificities among coronavirus main proteases","volume":"83","author":"Hegyi","year":"2002","journal-title":"J. Gen. Virol."},{"issue":"1","key":"10.1016\/j.cbi.2025.111620_bib4","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s42003-020-01577-x","article-title":"Identification of 3-chymotrypsin like protease (3CLpro) inhibitors as potential anti-SARS-CoV-2 agents","volume":"4","author":"Mody","year":"2021","journal-title":"J. Commun. Biol."},{"issue":"1","key":"10.1016\/j.cbi.2025.111620_bib5","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1080\/13880209.2023.2241518","article-title":"Recent advances towards natural plants as potential inhibitors of SARS-Cov-2 targets","volume":"61","author":"He","year":"2023","journal-title":"J. Pharm. Biol."},{"issue":"10","key":"10.1016\/j.cbi.2025.111620_bib6","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1002\/ptr.7580","article-title":"Promising natural products against SARS-CoV-2: structure, function, and clinical trials","volume":"36","author":"Zhao","year":"2022","journal-title":"J. Phytother Res."},{"issue":"6575","key":"10.1016\/j.cbi.2025.111620_bib7","first-page":"1586","article-title":"An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19","volume":"374","author":"Owen","year":"2021","journal-title":"J. Science"},{"issue":"6489","key":"10.1016\/j.cbi.2025.111620_bib8","first-page":"409","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":"J. Science"},{"key":"10.1016\/j.cbi.2025.111620_bib9","article-title":"In vitro and in vivo evaluation of the main protease inhibitor FB2001 against SARS-CoV-2","volume":"208","author":"Shang","year":"2022","journal-title":"J. Antivir. Res."},{"issue":"23","key":"10.1016\/j.cbi.2025.111620_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."},{"issue":"1","key":"10.1016\/j.cbi.2025.111620_bib11","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1038\/s41467-020-16954-7","article-title":"Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography","volume":"11","author":"Kneller","year":"2020","journal-title":"J. Nat. Commun."},{"issue":"4","key":"10.1016\/j.cbi.2025.111620_bib12","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1002\/med.21783","article-title":"What coronavirus 3C-like protease tells us: from structure, substrate selectivity, to inhibitor design","volume":"41","author":"Xiong","year":"2021","journal-title":"J. Med. Res. Rev."},{"issue":"15","key":"10.1016\/j.cbi.2025.111620_bib13","doi-asserted-by":"crossref","first-page":"4568","DOI":"10.1021\/bi036022q","article-title":"3C-like proteinase from SARS coronavirus catalyzes substrate hydrolysis by a general base mechanism","volume":"43","author":"Huang","year":"2004","journal-title":"J. Biochemistry"},{"issue":"6542","key":"10.1016\/j.cbi.2025.111620_bib14","first-page":"642","article-title":"X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease","volume":"372","author":"G\u00fcnther","year":"2021","journal-title":"J. Science"},{"issue":"19","key":"10.1016\/j.cbi.2025.111620_bib15","doi-asserted-by":"crossref","first-page":"12500","DOI":"10.1021\/acs.jmedchem.2c01005","article-title":"Targeting SARS-CoV-2 main protease for treatment of COVID-19: covalent inhibitors structure-activity relationship insights and evolution perspectives","volume":"65","author":"La","year":"2022","journal-title":"J. Med. Chem."},{"issue":"1","key":"10.1016\/j.cbi.2025.111620_bib16","doi-asserted-by":"crossref","first-page":"6463","DOI":"10.1038\/s41467-023-42102-y","article-title":"Structure-based development and preclinical evaluation of the SARS-CoV-2 3C-like protease inhibitor simnotrelvir","volume":"14","author":"Jiang","year":"2023","journal-title":"J. Nat. Commun."},{"issue":"4","key":"10.1016\/j.cbi.2025.111620_bib17","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/s41564-024-01618-9","article-title":"Preclinical evaluation of the SARS-CoV-2 Mpro inhibitor RAY1216 shows improved pharmacokinetics compared with nirmatrelvir","volume":"9","author":"Chen","year":"2024","journal-title":"J. Nat. Microbiol."},{"issue":"52","key":"10.1016\/j.cbi.2025.111620_bib18","doi-asserted-by":"crossref","first-page":"21883","DOI":"10.1021\/jacs.0c10770","article-title":"Proton-coupled conformational activation of SARS coronavirus main proteases and opportunity for designing small-molecule broad-spectrum targeted covalent inhibitors","volume":"142","author":"Verma","year":"2020","journal-title":"J. Am. Chem. Soc."},{"issue":"3","key":"10.1016\/j.cbi.2025.111620_bib19","article-title":"The SARS-CoV-2 main protease (Mpro): structure, function, and emerging therapies for COVID-19","volume":"3","author":"Hu","year":"2022","journal-title":"J. MedComm"},{"key":"10.1016\/j.cbi.2025.111620_bib20","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.ijbiomac.2021.07.167","article-title":"Flavonoids in Ampelopsis grossedentata as covalent inhibitors of SARS-CoV-2 3CLpro: inhibition potentials, covalent binding sites and inhibitory mechanisms","volume":"187","author":"Xiong","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.cbi.2025.111620_bib21","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ejmech.2014.03.008","article-title":"Discovery of N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement","volume":"77","author":"Li","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.cbi.2025.111620_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113583","article-title":"Discovery of chiral N-2'-aryletheryl-1'-alkoxy-ethyl substituted arylisoquinolones with anti-inflammatory activity from the nucleophilic addition reactions of the thiophenols and oxazolinium","volume":"222","author":"Li","year":"2021","journal-title":"Eur. J. Med. Chem."},{"issue":"17","key":"10.1016\/j.cbi.2025.111620_bib23","doi-asserted-by":"crossref","first-page":"11840","DOI":"10.1021\/acs.jmedchem.2c00937","article-title":"Chemo- and site-selective lysine modification of peptides and proteins under native conditions using the water-soluble zolinium","volume":"65","author":"Sun","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.cbi.2025.111620_bib24","article-title":"Discovery of naturally occurring inhibitors against SARS-CoV-2 3CLpro from Ginkgo biloba leaves via large-scale screening","volume":"152","author":"Xiong","year":"2021","journal-title":"J. Fitoterapia"},{"key":"10.1016\/j.cbi.2025.111620_bib25","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.ijbiomac.2021.04.129","article-title":"Identification of vitamin K3 and its analogues as covalent inhibitors of SARS-CoV-2 3CLpro","volume":"183","author":"Wang","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"issue":"2","key":"10.1016\/j.cbi.2025.111620_bib26","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/toxsci\/kfv190","article-title":"Identification of endogenous site-specific covalent binding of catechol estrogens to serum proteins in human blood","volume":"148","author":"Fang","year":"2015","journal-title":"J. Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.cbi.2025.111620_bib27","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s42004-024-01279-z","article-title":"Development of ketalized unsaturated saccharides as multifunctional cysteine-targeting covalent warheads","volume":"7","author":"Dong","year":"2024","journal-title":"J. Commun. Chem."},{"issue":"21","key":"10.1016\/j.cbi.2025.111620_bib28","doi-asserted-by":"crossref","first-page":"12725","DOI":"10.1021\/acs.jmedchem.0c01063","article-title":"Discovery of ketone-based covalent inhibitors of coronavirus 3CL proteases for the potential therapeutic treatment of COVID-19","volume":"63","author":"Hoffman","year":"2020","journal-title":"J. Med. Chem."},{"issue":"20","key":"10.1016\/j.cbi.2025.111620_bib29","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1016\/S0960-894X(02)00619-4","article-title":"General solid-phase method to prepare novel cyclic ketone inhibitors of the cysteine protease cruzain","volume":"12","author":"Huang","year":"2002","journal-title":"J. Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.cbi.2025.111620_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116410","article-title":"Discovery of novel amide derivatives as potent quorum sensing inhibitors of Pseudomonas aeruginosa","volume":"271","author":"He","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.cbi.2025.111620_bib31","series-title":"Liver Pathophysiology: Therapies and Antioxidants","first-page":"391","article-title":"Hepatic metabolism in liver health and disease","author":"Liu","year":"2017"},{"issue":"4","key":"10.1016\/j.cbi.2025.111620_bib32","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2","volume":"5","year":"2020","journal-title":"J. Nat. Microbiol."},{"key":"10.1016\/j.cbi.2025.111620_bib34","article-title":"Reversible covalent inhibitors suppress enterovirus 71 infection by targeting the 3C protease","volume":"192","author":"Liu","year":"2021","journal-title":"J. Antivir. Res."},{"issue":"4","key":"10.1016\/j.cbi.2025.111620_bib35","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jbt.20178","article-title":"Human carboxylesterases and their role in xenobiotic and endobiotic metabolism","volume":"21","author":"Ross","year":"2007","journal-title":"J. Biochem. Mol. Toxicol."},{"issue":"7542","key":"10.1016\/j.cbi.2025.111620_bib36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature14259","article-title":"Notum deacylates wnt proteins to suppress signalling activity","volume":"519","author":"Kakugawa","year":"2015","journal-title":"J. Nature"},{"issue":"3","key":"10.1016\/j.cbi.2025.111620_bib37","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.pbi.2006.03.002","article-title":"Green leaf volatiles: hydroperoxide lyase pathway of oxylipin metabolism","volume":"9","author":"Matsui","year":"2006","journal-title":"J. Curr. Opin. Plant Biol."},{"issue":"5626","key":"10.1016\/j.cbi.2025.111620_bib38","first-page":"1763","article-title":"Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs","volume":"300","author":"Anand","year":"2003","journal-title":"J. Science"},{"key":"10.1016\/j.cbi.2025.111620_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2025.139590","article-title":"Cys44 of SARS-CoV-2 3CLpro affects its catalytic activity","volume":"295","author":"Iacobucci","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"issue":"8","key":"10.1016\/j.cbi.2025.111620_bib40","article-title":"3-chymotrypsin-like protease in SARS-CoV-2","volume":"44","author":"Al","year":"2024","journal-title":"J. Biosci. Rep."},{"issue":"4","key":"10.1016\/j.cbi.2025.111620_bib41","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0031-6997(24)01340-1","article-title":"Role of pharmacokinetics and metabolism in drug discovery and development","volume":"49","author":"Lin","year":"1997","journal-title":"J. Pharmacol. Rev."},{"issue":"1","key":"10.1016\/j.cbi.2025.111620_bib42","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1021\/tx7002273","article-title":"Metabolism and toxicity of drugs. Two decades of progress in industrial drug metabolism","volume":"21","author":"Baillie","year":"2008","journal-title":"J. Chem. Res. Toxicol."},{"issue":"19","key":"10.1016\/j.cbi.2025.111620_bib43","doi-asserted-by":"crossref","first-page":"10969","DOI":"10.1093\/nar\/gkx818","article-title":"Impact of enhanced metabolic stability on pharmacokinetics and pharmacodynamics of GalNAc-siRNA conjugates","volume":"45","author":"Nair","year":"2017","journal-title":"J. Nucleic Acids Res."}],"container-title":["Chemico-Biological Interactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009279725002509?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009279725002509?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:17:22Z","timestamp":1778876242000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009279725002509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":42,"alternative-id":["S0009279725002509"],"URL":"https:\/\/doi.org\/10.1016\/j.cbi.2025.111620","relation":{},"ISSN":["0009-2797"],"issn-type":[{"value":"0009-2797","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Thiazole-fused thiazoliniums with ketone warheads as covalent inhibitors targeting Cys44 of SARS-CoV-2 3CLpro","name":"articletitle","label":"Article Title"},{"value":"Chemico-Biological Interactions","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cbi.2025.111620","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"111620"}}