{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:23:10Z","timestamp":1793748190774,"version":"4.6.1"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"am","delay-in-days":269,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI164088"],"award-info":[{"award-number":["R21AI164088"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007904","name":"Texas A and M University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007904","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30 GM124169-01"],"award-info":[{"award-number":["P30 GM124169-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R21EB032983"],"award-info":[{"award-number":["R21EB032983"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006132","name":"Office of Science","doi-asserted-by":"publisher","award":["DE-AC02-05CH11231"],"award-info":[{"award-number":["DE-AC02-05CH11231"]}],"id":[{"id":"10.13039\/100006132","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["A-1715"],"award-info":[{"award-number":["A-1715"]}],"id":[{"id":"10.13039\/100000928","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":[[2022,10]]},"DOI":"10.1016\/j.ejmech.2022.114570","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T11:35:16Z","timestamp":1656329716000},"page":"114570","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":43,"special_numbering":"C","title":["A multi-pronged evaluation of aldehyde-based tripeptidyl main protease inhibitors as SARS-CoV-2 antivirals"],"prefix":"10.1016","volume":"240","author":[{"given":"Yuying","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai S.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Zachary","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugendar R.","family":"Alugubelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namir","family":"Shaabani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erol C.","family":"Vatansever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu R.","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Chuan","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaustav","family":"Khatua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren R.","family":"Blankenship","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banumathi","family":"Sankaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshe Ray","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"7807","key":"10.1016\/j.ejmech.2022.114570_bib1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"Lan","year":"2020","journal-title":"Nature"},{"issue":"6485","key":"10.1016\/j.ejmech.2022.114570_bib2","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"issue":"4","key":"10.1016\/j.ejmech.2022.114570_bib3","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.cell.2020.04.011","article-title":"The architecture of SARS-CoV-2 transcriptome","volume":"181","author":"Kim","year":"2020","journal-title":"Cell"},{"issue":"7798","key":"10.1016\/j.ejmech.2022.114570_bib4","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"issue":"5","key":"10.1016\/j.ejmech.2022.114570_bib5","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/cbic.202000047","article-title":"Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV","volume":"21","author":"Morse","year":"2020","journal-title":"Chembiochem"},{"issue":"6497","key":"10.1016\/j.ejmech.2022.114570_bib6","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"},{"issue":"1","key":"10.1016\/j.ejmech.2022.114570_bib7","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1038\/s41467-020-18233-x","article-title":"Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease","volume":"11","author":"Fu","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2022.114570_bib8","article-title":"Design, synthesis, and biological evaluation of peptidomimetic aldehydes as broad-spectrum inhibitors against enterovirus and SARS-CoV-2","author":"Dai","year":"2021","journal-title":"J. Med. Chem."},{"issue":"6536","key":"10.1016\/j.ejmech.2022.114570_bib9","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"},{"issue":"21","key":"10.1016\/j.ejmech.2022.114570_bib10","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":"8","key":"10.1016\/j.ejmech.2022.114570_bib11","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41422-020-0356-z","article-title":"Boceprevir, GC-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."},{"issue":"50","key":"10.1016\/j.ejmech.2022.114570_bib12","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abe0751","article-title":"Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against M(pro) and cathepsin L","volume":"6","author":"Sacco","year":"2020","journal-title":"Sci. Adv."},{"issue":"6","key":"10.1016\/j.ejmech.2022.114570_bib13","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/cmdc.202000924","article-title":"A quick route to multiple highly potent SARS-CoV-2 main protease inhibitors","volume":"16","author":"Yang","year":"2021","journal-title":"ChemMedChem"},{"issue":"1","key":"10.1016\/j.ejmech.2022.114570_bib14","article-title":"MPI8 is potent against SARS-CoV-2 by inhibiting dually and selectively the SARS-CoV-2 main protease and the host cathepsin L","volume":"17","author":"Ma","year":"2022","journal-title":"ChemMedChem"},{"issue":"1","key":"10.1016\/j.ejmech.2022.114570_bib15","doi-asserted-by":"crossref","first-page":"5047","DOI":"10.1038\/s41467-020-18709-w","article-title":"Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease","volume":"11","author":"Douangamath","year":"2020","journal-title":"Nat. Commun."},{"issue":"12","key":"10.1016\/j.ejmech.2022.114570_bib16","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1021\/acsmedchemlett.0c00521","article-title":"Identification of 14 known drugs as inhibitors of the main protease of SARS-CoV-2","volume":"11","author":"Ghahremanpour","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"issue":"7811","key":"10.1016\/j.ejmech.2022.114570_bib17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-020-2223-y","article-title":"Structure of M(pro) from SARS-CoV-2 and discovery of its inhibitors","volume":"582","author":"Jin","year":"2020","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.ejmech.2022.114570_bib18","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41594-020-0440-6","article-title":"Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur","volume":"27","author":"Jin","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"issue":"6","key":"10.1016\/j.ejmech.2022.114570_bib19","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1021\/acsptsci.0c00130","article-title":"Ebselen, disulfiram, carmofur, PX-12, tideglusib, and shikonin are nonspecific promiscuous SARS-CoV-2 main protease inhibitors","volume":"3","author":"Ma","year":"2020","journal-title":"ACS Pharmacol Transl Sci"},{"issue":"557","key":"10.1016\/j.ejmech.2022.114570_bib20","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abc5332","article-title":"3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice","volume":"12","author":"Rathnayake","year":"2020","journal-title":"Sci. Transl. Med."},{"issue":"5","key":"10.1016\/j.ejmech.2022.114570_bib21","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1021\/acsptsci.0c00108","article-title":"Identification of SARS-CoV-2 3CL protease inhibitors by a quantitative high-throughput screening","volume":"3","author":"Zhu","year":"2020","journal-title":"ACS Pharmacol Transl Sci"},{"issue":"6542","key":"10.1016\/j.ejmech.2022.114570_bib22","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1126\/science.abf7945","article-title":"X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease","volume":"372","author":"Gunther","year":"2021","journal-title":"Science"},{"issue":"1","key":"10.1016\/j.ejmech.2022.114570_bib23","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41467-021-20900-6","article-title":"A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication","volume":"12","author":"Hattori","year":"2021","journal-title":"Nat. Commun."},{"issue":"4","key":"10.1016\/j.ejmech.2022.114570_bib24","doi-asserted-by":"crossref","first-page":"e02577","DOI":"10.1128\/AAC.02577-20","article-title":"Kinetic characterization and inhibitor screening for the proteases leading to identification of drugs against SARS-CoV-2","volume":"65","author":"Kuo","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"issue":"2","key":"10.1016\/j.ejmech.2022.114570_bib25","doi-asserted-by":"crossref","DOI":"10.3390\/v13020174","article-title":"Crystal structure of SARS-CoV-2 main protease in complex with the non-covalent inhibitor ML188","volume":"13","author":"Lockbaum","year":"2021","journal-title":"Viruses"},{"issue":"12","key":"10.1016\/j.ejmech.2022.114570_bib26","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.chembiol.2021.05.018","article-title":"An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 M(pro) inhibitor","volume":"28","author":"Zaidman","year":"2021","journal-title":"Cell Chem Biol"},{"issue":"3","key":"10.1016\/j.ejmech.2022.114570_bib27","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."},{"issue":"10","key":"10.1016\/j.ejmech.2022.114570_bib28","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2012201118","article-title":"Bepridil is potent against SARS-CoV-2 in vitro","volume":"118","author":"Vatansever","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"6575","key":"10.1016\/j.ejmech.2022.114570_bib29","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"},{"key":"10.1016\/j.ejmech.2022.114570_bib30","article-title":"Evolutionary and structural insights about potential SARS-CoV-2 evasion of nirmatrelvir","author":"Yang","year":"2022","journal-title":"J. Med. Chem."},{"issue":"2","key":"10.1016\/j.ejmech.2022.114570_bib31","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1021\/acscentsci.1c00910","article-title":"Evaluation of SARS-CoV-2 main protease inhibitors using a novel cell-based assay","volume":"8","author":"Cao","year":"2022","journal-title":"ACS Cent. Sci."},{"issue":"49","key":"10.1016\/j.ejmech.2022.114570_bib32","doi-asserted-by":"crossref","first-page":"20697","DOI":"10.1021\/jacs.1c08060","article-title":"Discovery of di- and trihaloacetamides as covalent SARS-CoV-2 main protease inhibitors with high target specificity","volume":"143","author":"Ma","year":"2021","journal-title":"J. Am. Chem. Soc."},{"issue":"14","key":"10.1016\/j.ejmech.2022.114570_bib33","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02374-20","article-title":"Inhibitors of coronavirus 3CL proteases protect cells from protease-mediated cytotoxicity","volume":"95","author":"Resnick","year":"2021","journal-title":"J. Virol."},{"key":"10.1016\/j.ejmech.2022.114570_bib34","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1038\/s41467-021-22362-2","article-title":"Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors","volume":"12","author":"Iketani","year":"2021","journal-title":"Nat. Commun."},{"issue":"2","key":"10.1016\/j.ejmech.2022.114570_bib35","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"issue":"2","key":"10.1016\/j.ejmech.2022.114570_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108254","article-title":"Furin inhibitors block SARS-CoV-2 spike protein cleavage to suppress virus production and cytopathic effects","volume":"33","author":"Cheng","year":"2020","journal-title":"Cell Rep."},{"issue":"1","key":"10.1016\/j.ejmech.2022.114570_bib37","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41392-021-00558-8","article-title":"Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development","volume":"6","author":"Zhao","year":"2021","journal-title":"Signal Transduct Tar"},{"key":"10.1016\/j.ejmech.2022.114570_bib38","article-title":"The N-terminal carbamate is key to high cellular and antiviral potency for boceprevir-based SARS-CoV-2 main protease inhibitors","author":"Alugubelli","year":"2021","journal-title":"bioRxiv"},{"issue":"6","key":"10.1016\/j.ejmech.2022.114570_bib39","first-page":"469","article-title":"Analysis of cell viability by the MTT assay","volume":"2018","author":"Kumar","year":"2018","journal-title":"Cold Spring Harb. Protoc."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342200472X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342200472X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:40:16Z","timestamp":1759329616000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S022352342200472X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":39,"alternative-id":["S022352342200472X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114570","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A multi-pronged evaluation of aldehyde-based tripeptidyl main protease inhibitors as SARS-CoV-2 antivirals","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114570","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"114570"}}