{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:18:32Z","timestamp":1787750312011,"version":"build-2784847793"},"reference-count":48,"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":[[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\/501100001663","name":"Volkswagen Foundation","doi-asserted-by":"publisher","award":["9A836"],"award-info":[{"award-number":["9A836"]}],"id":[{"id":"10.13039\/501100001663","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.2022.114585","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T11:37:36Z","timestamp":1657539456000},"page":"114585","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"special_numbering":"C","title":["Discovery of potent benzoxaborole inhibitors against SARS-CoV-2 main and dengue virus proteases"],"prefix":"10.1016","volume":"240","author":[{"given":"Nikos","family":"K\u00fchl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila M.","family":"Leuthold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3522-9182","authenticated-orcid":false,"given":"Christian D.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2022.114585_bib1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijid.2020.03.004","article-title":"The SARS-CoV-2 outbreak: what we know","volume":"94","author":"Wu","year":"2020","journal-title":"Int. J. Infect. Dis."},{"issue":"5","key":"10.1016\/j.ejmech.2022.114585_bib2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time","volume":"20","author":"Dong","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.ejmech.2022.114585_bib3","series-title":"An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19","first-page":"1586","volume":"374","author":"Owen","year":"2021"},{"issue":"9","key":"10.1016\/j.ejmech.2022.114585_bib4","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."},{"issue":"7446","key":"10.1016\/j.ejmech.2022.114585_bib5","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"issue":"12","key":"10.1016\/j.ejmech.2022.114585_bib6","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1038\/nrmicro2460","article-title":"Dengue: a continuing global threat","volume":"8","author":"Guzman","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"issue":"3","key":"10.1016\/j.ejmech.2022.114585_bib7","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1128\/CMR.11.3.480","article-title":"Dengue and dengue hemorrhagic fever","volume":"11","author":"Gubler","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"issue":"22","key":"10.1016\/j.ejmech.2022.114585_bib8","doi-asserted-by":"crossref","first-page":"11348","DOI":"10.1021\/cr500233q","article-title":"Biochemistry and medicinal chemistry of the dengue virus protease","volume":"114","author":"Nitsche","year":"2014","journal-title":"Chem. Rev."},{"issue":"17","key":"10.1016\/j.ejmech.2022.114585_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2020.127377","article-title":"The SARS-CoV-2 main protease as drug target","volume":"30","author":"Ullrich","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"3","key":"10.1016\/j.ejmech.2022.114585_bib10","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/med.10043","article-title":"Boronic acid compounds as potential pharmaceutical agents","volume":"23","author":"Yang","year":"2003","journal-title":"Med. Res. Rev."},{"issue":"7","key":"10.1016\/j.ejmech.2022.114585_bib11","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1021\/cr608202m","article-title":"Boron containing compounds as protease inhibitors","volume":"112","author":"Smoum","year":"2012","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2022.114585_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112270","article-title":"Design and discovery of boronic acid drugs","volume":"195","author":"Plescia","year":"2020","journal-title":"Eur. J. Med. Chem."},{"issue":"17","key":"10.1016\/j.ejmech.2022.114585_bib13","doi-asserted-by":"crossref","first-page":"4906","DOI":"10.1021\/bi0361766","article-title":"Identification of novel inhibitors of the SARS coronavirus main protease 3CLpro","volume":"43","author":"Bacha","year":"2004","journal-title":"Biochemistry"},{"issue":"6","key":"10.1016\/j.ejmech.2022.114585_bib14","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1080\/13543776.2018.1473379","article-title":"Benzoxaborole compounds for therapeutic uses: a patent review (2010- 2018)","volume":"28","author":"Nocentini","year":"2018","journal-title":"Expert Opin. Ther. Pat."},{"issue":"13","key":"10.1016\/j.ejmech.2022.114585_bib15","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1007\/s40265-014-0276-7","article-title":"Tavaborole: first global approval","volume":"74","author":"Markham","year":"2014","journal-title":"Drugs"},{"issue":"9","key":"10.1016\/j.ejmech.2022.114585_bib16","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1080\/14656566.2019.1604688","article-title":"Evaluating crisaborole as a treatment option for atopic dermatitis","volume":"20","author":"Ramachandran","year":"2019","journal-title":"Expet Opin. Pharmacother."},{"issue":"38","key":"10.1016\/j.ejmech.2022.114585_bib17","first-page":"9616","article-title":"Clinical and veterinary trypanocidal benzoxaboroles target","volume":"115","author":"Wall","year":"2018","journal-title":"CPSF3"},{"issue":"1","key":"10.1016\/j.ejmech.2022.114585_bib18","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.bmcl.2005.09.062","article-title":"Peptide inhibitors of dengue virus NS3 protease. Part 1: Warhead","volume":"16","author":"Yin","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"1","key":"10.1016\/j.ejmech.2022.114585_bib19","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1021\/acs.jmedchem.6b01021","article-title":"Peptide\u2013boronic acid inhibitors of flaviviral proteases: medicinal chemistry and structural biology","volume":"60","author":"Nitsche","year":"2017","journal-title":"J. Med. Chem."},{"issue":"6298","key":"10.1016\/j.ejmech.2022.114585_bib20","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1126\/science.aag2419","article-title":"Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor","volume":"353","author":"Lei","year":"2016","journal-title":"Science"},{"issue":"24","key":"10.1016\/j.ejmech.2022.114585_bib21","doi-asserted-by":"crossref","first-page":"7317","DOI":"10.1016\/j.bmcl.2010.10.071","article-title":"Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease","volume":"20","author":"Ding","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"7","key":"10.1016\/j.ejmech.2022.114585_bib22","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/j.bmcl.2011.02.006","article-title":"Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties","volume":"21","author":"Li","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"12","key":"10.1016\/j.ejmech.2022.114585_bib23","doi-asserted-by":"crossref","first-page":"3550","DOI":"10.1016\/j.bmcl.2010.04.129","article-title":"Synthesis and evaluation of novel \u03b1-amino cyclic boronates as inhibitors of HCV NS3 protease","volume":"20","author":"Li","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"21","key":"10.1016\/j.ejmech.2022.114585_bib24","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1016\/S0960-894X(02)00682-0","article-title":"P1 Phenethyl peptide boronic acid inhibitors of HCV NS3 protease","volume":"12","author":"Priestley","year":"2002","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"1","key":"10.1016\/j.ejmech.2022.114585_bib25","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.bmcl.2008.10.124","article-title":"Potent inhibitors of HCV-NS3 protease derived from boronic acids","volume":"19","author":"Venkatraman","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"43","key":"10.1016\/j.ejmech.2022.114585_bib26","doi-asserted-by":"crossref","first-page":"14015","DOI":"10.1021\/jacs.8b07366","article-title":"Sub-picomolar inhibition of HIV-1 protease with a boronic acid","volume":"140","author":"Windsor","year":"2018","journal-title":"J. Am. Chem. Soc."},{"issue":"15","key":"10.1016\/j.ejmech.2022.114585_bib27","doi-asserted-by":"crossref","first-page":"8179","DOI":"10.1021\/acs.jmedchem.0c00413","article-title":"A new class of dengue and west nile virus protease inhibitors with submicromolar activity in reporter gene DENV-2 protease and viral replication assays","volume":"63","author":"K\u00fchl","year":"2020","journal-title":"J. Med. Chem."},{"issue":"8","key":"10.1016\/j.ejmech.2022.114585_bib28","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1021\/acs.jmedchem.0c02042","article-title":"Beyond basicity: discovery of nonbasic DENV-2 protease inhibitors with potent activity in cell culture","volume":"64","author":"K\u00fchl","year":"2021","journal-title":"J. Med. Chem."},{"issue":"6","key":"10.1016\/j.ejmech.2022.114585_bib29","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1021\/jp9086283","article-title":"Influence of the substituents on the structure and properties of benzoxaboroles","volume":"114","author":"Adamczyk-Wo\u017aniak","year":"2010","journal-title":"J. Phys. Chem."},{"issue":"2","key":"10.1016\/j.ejmech.2022.114585_bib30","first-page":"199","article-title":"Amination-reduction reaction as simple protocol for potential boronic molecular receptors. Insight in supramolecular structure directed by weak interactions","volume":"9","author":"Adamczyk-Wo\u017aniak","year":"2011","journal-title":"Cent. Eur. J. Chem."},{"issue":"20","key":"10.1016\/j.ejmech.2022.114585_bib31","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1055\/s-0033-1339550","article-title":"A convenient and efficient synthesis of dipeptidyl benzoxaboroles and their peptidomimetics","volume":"45","author":"Fu","year":"2013","journal-title":"Synthesis"},{"key":"10.1016\/j.ejmech.2022.114585_bib32","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.biochi.2020.04.014","article-title":"Conformational selection in the flaviviral NS2B-NS3 protease","volume":"174","author":"Behnam","year":"2020","journal-title":"Biochimie"},{"issue":"17","key":"10.1016\/j.ejmech.2022.114585_bib33","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1002\/cmdc.201700329","article-title":"What are we missing? The detergent triton X-100 Added to avoid compound aggregation can affect assay results in an unpredictable manner","volume":"12","author":"Ehlert","year":"2017","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2022.114585_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113695","article-title":"Amidoxime prodrugs convert to potent cell-active multimodal inhibitors of the dengue virus protease","volume":"224","author":"Swarbrick","year":"2021","journal-title":"Eur. J. Med. Chem."},{"issue":"9","key":"10.1016\/j.ejmech.2022.114585_bib35","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1177\/24725552211020681","article-title":"Efficiency improvements and discovery of new substrates for a SARS-CoV-2 main protease FRET assay","volume":"26","author":"Dra\u017ei\u0107","year":"2021","journal-title":"SLAS disc. : adv. life sci. R & D"},{"issue":"23","key":"10.1016\/j.ejmech.2022.114585_bib36","doi-asserted-by":"crossref","first-page":"9354","DOI":"10.1021\/acs.jmedchem.5b01441","article-title":"Discovery of nanomolar dengue and west nile virus protease inhibitors containing a 4-benzyloxyphenylglycine residue","volume":"58","author":"Behnam","year":"2015","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2022.114585_bib37","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1039\/D0MD00367K","article-title":"Repurposing the HCV NS3\u20134A protease drug boceprevir as COVID-19 therapeutics","volume":"12","author":"Oerlemans","year":"2021","journal-title":"RSC Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114585_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2021.116415","article-title":"A short survey of Dengue protease inhibitor development in the past 6 years (2015-2020) with an emphasis on similarities between DENV and SARS-CoV-2 proteases","author":"Murtuja","year":"2021","journal-title":"Biorg. Med. Chem."},{"issue":"6","key":"10.1016\/j.ejmech.2022.114585_bib39","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1016\/j.jinf.2020.08.009","article-title":"Emergence of co-infection of COVID-19 and dengue: a serious public health threat","volume":"81","author":"Saddique","year":"2020","journal-title":"J. Infect."},{"issue":"6","key":"10.1016\/j.ejmech.2022.114585_bib40","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":"7","key":"10.1016\/j.ejmech.2022.114585_bib41","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1007\/s11095-007-9517-8","article-title":"A novel design of artificial membrane for improving the PAMPA model","volume":"25","author":"Chen","year":"2008","journal-title":"Pharm. Res. (N. Y.)"},{"issue":"7","key":"10.1016\/j.ejmech.2022.114585_bib42","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1021\/jm970530e","article-title":"Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes","volume":"41","author":"Kansy","year":"1998","journal-title":"J. Med. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2022.114585_bib43","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/acs.jmedchem.9b00759","article-title":"Peptide-\u03b2-lactam inhibitors of dengue and west nile virus NS2B-NS3 protease display two distinct binding modes","volume":"63","author":"Dra\u017ei\u0107","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114585_bib44","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2021.116412","article-title":"The spectrum between substrates and inhibitors: pinpointing the binding mode of dengue protease ligands with modulated basicity and hydrophobicity","author":"Dra\u017ei\u0107","year":"2021","journal-title":"Biorg. Med. Chem."},{"issue":"26","key":"10.1016\/j.ejmech.2022.114585_bib45","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.1016\/j.tet.2016.03.038","article-title":"Synthesis and evaluation of functionalized benzoboroxoles as potential anti-tuberculosis agents","volume":"72","author":"Alam","year":"2016","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2022.114585_bib46","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jorganchem.2015.06.021","article-title":"Synthesis and evaluation of functionalized aminobenzoboroxoles as potential anti-cancer agents","volume":"798","author":"Suman","year":"2015","journal-title":"J. Organomet. Chem."},{"issue":"80","key":"10.1016\/j.ejmech.2022.114585_bib47","doi-asserted-by":"crossref","first-page":"11983","DOI":"10.1039\/C6CC06399C","article-title":"Benzoxaborole as a new chemotype for carbonic anhydrase inhibition","volume":"52","author":"Alterio","year":"2016","journal-title":"Chem. Commun."},{"issue":"15","key":"10.1016\/j.ejmech.2022.114585_bib48","doi-asserted-by":"crossref","first-page":"8026","DOI":"10.1128\/JVI.00787-15","article-title":"Dengue virus inhibition of autophagic flux and dependency of viral replication on proteasomal degradation of the autophagy receptor p62","volume":"89","author":"Metz","year":"2015","journal-title":"J. Virol."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422004871?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422004871?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:45:40Z","timestamp":1759329940000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523422004871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":48,"alternative-id":["S0223523422004871"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114585","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":"Discovery of potent benzoxaborole inhibitors against SARS-CoV-2 main and dengue virus proteases","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114585","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":"114585"}}