{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:39:22Z","timestamp":1791639562755,"version":"4.3.4"},"reference-count":96,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2023,4]]},"DOI":"10.1016\/j.bioorg.2023.106408","type":"journal-article","created":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T11:06:35Z","timestamp":1675508795000},"page":"106408","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["Piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. In vitro antiviral activity evaluation against Zika and Dengue viruses"],"prefix":"10.1016","volume":"133","author":[{"given":"Mar\u00eda","family":"del Rosario Garc\u00eda-Lozano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Dragoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Gallego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Mazzotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"L\u00f3pez-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Boccuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Mart\u00ednez-Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Rodr\u00edguez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horacio","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Manuel Vega-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Antonio Del Campo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Vicenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Vega-Holm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Iglesias-Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2023.106408_b0005","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.coviro.2016.11.007","article-title":"Flavivirus transmission focusing on Zika","volume":"22","author":"Vasilakis","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"10.1016\/j.bioorg.2023.106408_b0010","doi-asserted-by":"crossref","DOI":"10.3390\/v12101090","article-title":"Delayed by design: Role of suboptimal signal peptidase processing of viral structural protein precursors in flaviviridae virus assembly","volume":"12","author":"Alzahrani","year":"2020","journal-title":"Viruses."},{"key":"10.1016\/j.bioorg.2023.106408_b0015","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.ejmech.2016.09.063","article-title":"Identification of fused bicyclic derivatives of pyrrolidine and imidazolidinone as dengue virus-2 NS2B-NS3 protease inhibitors","volume":"125","author":"Weng","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0020","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41564-020-0714-0","article-title":"The continued threat of emerging flaviviruses","volume":"5","author":"Pierson","year":"2020","journal-title":"Nat. Microbiol."},{"key":"10.1016\/j.bioorg.2023.106408_b0025","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1021\/acs.jmedchem.0c02070","article-title":"Synthesis, structure-activity relationships, and antiviral activity of allosteric inhibitors of flavivirus NS2B-NS3 protease","volume":"64","author":"Nie","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0030","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1016\/j.clinre.2020.101596","article-title":"Epidemiology of hepatitis C virus infection","volume":"45","author":"Roudot-Thoraval","year":"2021","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"10.1016\/j.bioorg.2023.106408_b0035","unstructured":"WHO 2022: Hepatitis C (2022) 2022. <https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-c> (Accessed: 2022-11-11)."},{"key":"10.1016\/j.bioorg.2023.106408_b0040","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.antiviral.2018.09.009","article-title":"The WHO R&D Blueprint: 2018 review of emerging infectious diseases requiring urgent research and development efforts","volume":"159","author":"Mehand","year":"2018","journal-title":"Antiviral Res"},{"key":"10.1016\/j.bioorg.2023.106408_b0045","unstructured":"WHO 2022: Dengue and severe dengue (2022) 2022. <https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and- severe-dengue> (Accessed: 2022-11-11)."},{"key":"10.1016\/j.bioorg.2023.106408_b0050","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/v12080829","article-title":"Dengue: a minireview","volume":"12","author":"Harapan","year":"2020","journal-title":"Viruses."},{"key":"10.1016\/j.bioorg.2023.106408_b0055","first-page":"1","article-title":"Potential role of flavivirus NS2B-NS3 proteases in viral pathogenesis and anti-flavivirus drug discovery employing animal cells and models","author":"Wahaab","year":"2022","journal-title":"A Review"},{"key":"10.1016\/j.bioorg.2023.106408_b0060","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/trstmh\/try070","article-title":"Implementing a dengue vaccination programme-who, where and how?","volume":"112","author":"Clapham","year":"2018","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"10.1016\/j.bioorg.2023.106408_b0065","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/S0140-6736(14)61060-6","article-title":"Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial","volume":"384","author":"Capeding","year":"2014","journal-title":"Lancet."},{"key":"10.1016\/j.bioorg.2023.106408_b0070","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/cmdc.201900533","article-title":"Design, synthesis and discovery of N, N\u2019-carbazoyl-aryl-urea inhibitors of Zika NS5 methyltransferase and virus replication","volume":"15","author":"Spizzichino","year":"2020","journal-title":"ChemMedChem."},{"key":"10.1016\/j.bioorg.2023.106408_b0075","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ympev.2017.09.015","article-title":"Protein backbone flexibility pattern is evolutionarily conserved in the Flaviviridae family: A case of NS3 protease in Flavivirus and Hepacivirus","volume":"118","author":"Palanisamy","year":"2018","journal-title":"Mol. Phylogenet. Evol."},{"key":"10.1016\/j.bioorg.2023.106408_b0080","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.antiviral.2013.09.013","article-title":"Ten years of dengue drug discovery: progress and prospects","volume":"100","author":"Lim","year":"2013","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0085","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-65489-w","article-title":"Zika virus NS3 protease pharmacophore anchor model and drug discovery","volume":"10","author":"Pathak","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2023.106408_b0090","doi-asserted-by":"crossref","DOI":"10.1186\/s12859-017-1957-5","article-title":"Pharmacophore anchor models of flaviviral NS3 proteases lead to drug repurposing for DENV infection","volume":"18","author":"Pathak","year":"2017","journal-title":"BMC Bioinform."},{"key":"10.1016\/j.bioorg.2023.106408_b0095","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.antiviral.2016.12.016","article-title":"Identification of novel small molecule inhibitors against NS2B\/NS3 serine protease from Zika virus","volume":"139","author":"Lee","year":"2017","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0100","doi-asserted-by":"crossref","first-page":"5432","DOI":"10.1021\/acs.jmedchem.6b00300","article-title":"New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine derivatives as potential inhibitors of adenovirus infection. synthesis, biological evaluation, and structure-activity relationships","volume":"59","author":"S\u00e1nchez-C\u00e9spedes","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2019.111840","article-title":"Optimization of piperazine-derived ureas privileged structures for effective antiadenovirus agents","volume":"185","author":"Mazzotta","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0110","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.ejmech.2016.10.043","article-title":"In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase","volume":"125","author":"Bassetto","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2019.126906","article-title":"Design, synthesis, and evaluation of novel 4-amino-2-(4-benzylpiperazin-1-yl)methylbenzonitrile compounds as Zika inhibitors","volume":"30","author":"Wang","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2023.106408_b0120","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/cbdd.12500","article-title":"Structure-guided discovery of a novel non-peptide inhibitor of dengue virus NS2B-NS3 protease","volume":"86","author":"Li","year":"2015","journal-title":"Chem. Biol. Drug Des."},{"key":"10.1016\/j.bioorg.2023.106408_b0125","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1016\/j.bmcl.2012.03.019","article-title":"Design, synthesis, and biological activity of novel 1,4-disubstituted piperidine\/piperazine derivatives as CCR5 antagonist-based HIV-1 entry inhibitors","volume":"22","author":"Dong","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2023.106408_b0130","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.bmcl.2011.10.122","article-title":"Inhibition of noroviruses by piperazine derivatives","volume":"22","author":"Dou","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2023.106408_b0135","doi-asserted-by":"crossref","first-page":"5059","DOI":"10.3390\/molecules18055059","article-title":"Novel substituted heteroaromatic piperazine and piperidine derivatives as inhibitors of human enterovirus 71 and coxsackievirus A16","volume":"18","author":"Zhang","year":"2013","journal-title":"Molecules."},{"key":"10.1016\/j.bioorg.2023.106408_b0140","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ejmech.2015.07.026","article-title":"Piperazine scaffold: A remarkable tool in generation of diverse pharmacological agents","volume":"102","author":"Shaquiquzzaman","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0145","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ejmech.2016.05.043","article-title":"Synthetic strategy and antiviral evaluation of diamide containing heterocycles targeting dengue and yellow fever virus","volume":"121","author":"Saudi","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0150","doi-asserted-by":"crossref","first-page":"479","DOI":"10.4172\/2161-0444.1000305","article-title":"Role of aryl urea containing compounds in medicinal chemistry","volume":"5","author":"Sikka","year":"2015","journal-title":"Med. Chem. (Los. Angeles)."},{"key":"10.1016\/j.bioorg.2023.106408_b0155","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00726-004-0146-9","article-title":"Pseudo-peptides derived from isomannide as potential inhibitors of serine proteases","volume":"28","author":"Muri","year":"2005","journal-title":"Amino Acids."},{"key":"10.1016\/j.bioorg.2023.106408_b0160","doi-asserted-by":"crossref","DOI":"10.1021\/acsinfecdis.0c00515","article-title":"Serinol-based benzoic acid esters as new scaffolds for the development of adenovirus infection inhibitors: design, synthesis, and in vitro biological evaluation","volume":"7","author":"Mazzotta","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.bioorg.2023.106408_b0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.105095","article-title":"Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol","volume":"114","author":"Mazzotta","year":"2021","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0170","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ejmech.2016.04.008","article-title":"Progress and prospects on DENV protease inhibitors","volume":"117","author":"Timiri","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0175","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1016\/j.bmc.2011.05.015","article-title":"Synthesis and biological evaluation of \u03b1-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture","volume":"19","author":"Steuer","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0180","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1021\/acs.jmedchem.0c01808","article-title":"The alpha keto amide moiety as a privileged motif in medicinal chemistry: current insights and emerging opportunities","volume":"64","author":"Robello","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0185","doi-asserted-by":"crossref","first-page":"7123","DOI":"10.1021\/acs.jmedchem.7b00731","article-title":"Discovery of novel and highly selective inhibitors of calpain for the treatment of Alzheimer\u2019s disease: 2-(3-phenyl-1H-pyrazol-1-yl)-nicotinamides","volume":"60","author":"Kling","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0190","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1039\/D0MD00288G","article-title":"Indole-a promising pharmacophore in recent antiviral drug discovery","volume":"11","author":"Dorababu","year":"2020","journal-title":"RSC Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0195","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1021\/acs.jmedchem.7b01337","article-title":"Inhibitors of HIV-1 attachment: the discovery and development of temsavir and its prodrug fostemsavir","volume":"61","author":"Meanwell","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0200","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms21165712","article-title":"Cinnamic acid derivatives and their biological efficacy","volume":"21","author":"Ruwizhi","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.bioorg.2023.106408_b0205","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/jbt.21715","article-title":"Cinnamic acid and cinnamaldehyde ameliorate cisplatin-induced splenotoxicity in rats","volume":"29","author":"Abd El-Raouf","year":"2015","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"10.1016\/j.bioorg.2023.106408_b0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2019.102951","article-title":"Design and synthesis of the novel oleanolic acid-cinnamic acid ester derivatives and glycyrrhetinic acid-cinnamic acid ester derivatives with cytotoxic properties","volume":"88","author":"Wang","year":"2019","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0215","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2019.116819","article-title":"Cinnamic acid rescues behavioral deficits in a mouse model of traumatic brain injury by targeting miR-455-3p\/HDAC2","volume":"235","author":"Guo","year":"2019","journal-title":"Life Sci."},{"key":"10.1016\/j.bioorg.2023.106408_b0220","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.antiviral.2017.07.018","article-title":"Cinnamic acid derivatives inhibit hepatitis C virus replication via the induction of oxidative stress","volume":"145","author":"Amano","year":"2017","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0225","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1021\/ol0489907","article-title":"Synthesis of BILN 2061, an HCV NS3 protease inhibitor with proven antiviral effect in humans","volume":"6","author":"Faucher","year":"2004","journal-title":"Org. Lett."},{"key":"10.1016\/j.bioorg.2023.106408_b0230","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2021.105117","article-title":"Cinnamic acid inhibits Zika virus by inhibiting RdRp activity","volume":"192","author":"Chen","year":"2021","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0235","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2019.111925","article-title":"Design, synthesis and discovery of andrographolide derivatives against Zika virus infection","volume":"187","author":"Li","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0240","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ejmech.2016.12.058","article-title":"2,8-bis(trifluoromethyl)quinoline analogs show improved anti-Zika virus activity, compared to mefloquine","volume":"127","author":"Barbosa-Lima","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0245","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.antiviral.2016.11.015","article-title":"Antiviral activities of selected antimalarials against dengue virus type 2 and Zika virus","volume":"137","author":"Balasubramanian","year":"2017","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0250","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.antiviral.2012.02.008","article-title":"Retro peptide-hybrids as selective inhibitors of the Dengue virus NS2B-NS3 protease","volume":"94","author":"Nitsche","year":"2012","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0255","doi-asserted-by":"crossref","first-page":"7318","DOI":"10.1016\/j.bmc.2011.10.061","article-title":"Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases","volume":"19","author":"Nitsche","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0260","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/molecules23030672","article-title":"Antiviral activity of novel quinoline derivatives against dengue virus serotype 2","volume":"23","author":"de la Guardia","year":"2018","journal-title":"Molecules."},{"key":"10.1016\/j.bioorg.2023.106408_b0265","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/cmdc.201800178","article-title":"Identification of broad-spectrum dengue\/zika virus replication inhibitors by functionalization of quinoline and 2,6-diaminopurine scaffolds","volume":"13","author":"Kaptein","year":"2018","journal-title":"ChemMedChem."},{"key":"10.1016\/j.bioorg.2023.106408_b0270","doi-asserted-by":"crossref","first-page":"6278","DOI":"10.1021\/jm300146f","article-title":"Discovery of novel small molecule inhibitors of dengue viral NS2B-NS3 protease using virtual screening and scaffold hopping","volume":"55","author":"Deng","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0275","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3851\/IMP3231","article-title":"A quinoline compound inhibits the replication of dengue virus serotypes 1\u20134 in Vero cells","volume":"23","author":"Beesetti","year":"2018","journal-title":"Antivir. Ther."},{"key":"10.1016\/j.bioorg.2023.106408_b0280","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1021\/acsinfecdis.1c00083","article-title":"Quinoline and quinazoline derivatives inhibit viral RNA synthesis by SARS-CoV-2 RdRp","volume":"7","author":"Zhao","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.bioorg.2023.106408_b0285","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.bmcl.2017.12.019","article-title":"Identification of novel small-molecule inhibitors of Zika virus infection","volume":"28","author":"Micewicz","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2023.106408_b0290","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2019.126626","article-title":"Optimization of 1,3-disubstituted urea-based inhibitors of Zika virus infection","volume":"29","author":"Khachatoorian","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2023.106408_b0295","article-title":"Exploration of piperazine-derived thioureas as antibacterial and anti-inflammatory agents. In vitro evaluation against clinical isolates of colistin-resistant Acinetobacter baumannii, Bioorganic Med","volume":"30","author":"Mazzotta","year":"2020","journal-title":"Chem. Lett."},{"key":"10.1016\/j.bioorg.2023.106408_b0300","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/nrd4366","article-title":"Phenotypic screening in cancer drug discovery-past, present and future","volume":"13","author":"Moffat","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.bioorg.2023.106408_b0305","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.antiviral.2017.04.015","article-title":"Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists","volume":"143","author":"Shiryaev","year":"2017","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0310","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1039\/C5MB00706B","article-title":"An updated evolutionary study of Flaviviridae NS3 helicase and NS5 RNA-dependent RNA polymerase reveals novel invariable motifs as potential pharmacological targets","volume":"12","author":"Papageorgiou","year":"2016","journal-title":"Mol. Biosyst."},{"key":"10.1016\/j.bioorg.2023.106408_b0315","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.antiviral.2015.03.014","article-title":"The flavivirus NS2B-NS3 protease-helicase as a target for antiviral drug development","volume":"118","author":"Luo","year":"2015","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0320","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.antiviral.2014.02.006","article-title":"Polymerases of hepatitis C viruses and flaviviruses: structural and mechanistic insights and drug development","volume":"105","author":"Caillet-Saguy","year":"2014","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0325","doi-asserted-by":"crossref","first-page":"4056","DOI":"10.1021\/acs.jmedchem.9b00091","article-title":"Discovery, optimization, and target identification of novel potent broad-spectrum antiviral inhibitors","volume":"62","author":"Yang","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0330","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1177\/2472555220911456","article-title":"Development of a cell-based immunodetection assay for simultaneous screening of antiviral compounds inhibiting zika and dengue virus replication","volume":"25","author":"Vicenti","year":"2020","journal-title":"SLAS Discov."},{"key":"10.1016\/j.bioorg.2023.106408_b0335","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1021\/acsmedchemlett.9b00681","article-title":"Exploring the Implication of DDX3X in DENV infection: discovery of the first-in-class DDX3X fluorescent inhibitor","volume":"11","author":"Brai","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2023.106408_b0340","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.virusres.2017.11.003","article-title":"Comparative analysis of different cell systems for Zika virus (ZIKV) propagation and evaluation of anti-ZIKV compounds in vitro","volume":"244","author":"Vicenti","year":"2018","journal-title":"Virus Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0345","first-page":"1","article-title":"The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication","volume":"7","author":"Sacramento","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2023.106408_b0350","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ejmech.2014.07.067","article-title":"Design, synthesis and antimycobacterial evaluation of 1-(4-(2- substitutedthiazol-4-yl)phenethyl)-4-(3-(4-substitutedpiperazin-1-yl)alkyl) piperazine hybrid analogues","volume":"84","author":"Nagesh","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0355","doi-asserted-by":"crossref","first-page":"W530","DOI":"10.1093\/nar\/gkab294","article-title":"PLIP 2021: Expanding the scope of the protein-ligand interaction profiler to DNA and RNA","volume":"49","author":"Adasme","year":"2021","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0360","unstructured":"L.L.C. Schr\u00f6dinger, The PyMOL Molecular Graphics System, Version 1.8, 2015, (n.d.)."},{"key":"10.1016\/j.bioorg.2023.106408_b0365","first-page":"e00172","article-title":"Avoiding drug resistance by substrate envelope-guided design: toward potent and Robust HCV NS3\/4A protease inhibitors","volume":"11","author":"Matthew","year":"2020","journal-title":"Mol. Biol. Physiol."},{"key":"10.1016\/j.bioorg.2023.106408_b0370","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27031076","article-title":"Hepatitis C virus NS3\/4A inhibition and host immunomodulation by tannins from terminalia chebula: a structural perspective","volume":"27","author":"Patil","year":"2022","journal-title":"Molecules."},{"key":"10.1016\/j.bioorg.2023.106408_b0375","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":"(80-.). 353","author":"Lei","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.bioorg.2023.106408_b0380","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.drudis.2019.10.014","article-title":"A drug-likeness toolbox facilitates ADMET study in drug discovery","volume":"25","author":"Jia","year":"2020","journal-title":"Drug Discov. Today."},{"key":"10.1016\/j.bioorg.2023.106408_b0385","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2012.09.019","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"64","author":"Lipinski","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.bioorg.2023.106408_b0390","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0395","first-page":"615","article-title":"A New Method for Calculating Partition Coefficients of Organic Compounds","volume":"13","author":"Wang","year":"1997","journal-title":"Acta Phys. - Chim. Sin."},{"key":"10.1016\/j.bioorg.2023.106408_b0400","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2023.106408_b0405","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.104841","article-title":"Design, synthesis and mechanistic study of new 1,2,4-triazole derivatives as antimicrobial agents","volume":"111","author":"Amin","year":"2021","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0410","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2020.103956","article-title":"Design, synthesis, mechanistic studies and in silico ADME predictions of benzimidazole derivatives as novel antifungal agents","volume":"101","author":"Morcoss","year":"2020","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0415","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1080\/14756366.2020.1740922","article-title":"2-Thiopyrimidine\/chalcone hybrids: design, synthesis, ADMET prediction, and anticancer evaluation as STAT3\/STAT5a inhibitors","volume":"35","author":"Lamie","year":"2020","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0420","unstructured":"S.K. Lee, Y. Kang, G.S. Chang, I.H. Lee, S.H. Park, J. Park, Bioinformatics and Molecular Design Research Center. Yonsei University, Seoul, (2017). <https:\/\/preadmet. bmdrc.kr>."},{"key":"10.1016\/j.bioorg.2023.106408_b0425","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2019.103307","article-title":"Design, synthesis, molecular modelling, ADME prediction and anti-hyperglycemic evaluation of new pyrazole-triazolopyrimidine hybrids as potent \u03b1-glucosidase inhibitors","volume":"93","author":"Pogaku","year":"2019","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2023.106408_b0430","unstructured":"J. S\u00e1nchez-C\u00e9spedes, M.E. Pach\u00f3n-Ib\u00e1\u00f1ez, J. Pach\u00f3n, P. Mart\u00ednez-Aguado, T. Cebrero-Cangueiro, J.M. ega-Per\u00e9z, F. Iglesias-Guerra, M. Vega-Holm, J.I. Candela-Lena, S. Mazzotta, Piperazine derivatives as antiviral agents with increased therapeutic activity; year of application. EP16382073.1 (23 February 2016), US 2019\/0308956 A1(10 October 2019)."},{"key":"10.1016\/j.bioorg.2023.106408_b0435","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1021\/acsinfecdis.8b00103","article-title":"New class of adjuvants enables lower dosing of colistin against acinetobacter baumannii","volume":"4","author":"Minrovic","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.bioorg.2023.106408_b0440","doi-asserted-by":"crossref","first-page":"6758","DOI":"10.1128\/JVI.72.8.6758-6769.1998","article-title":"Multiple enzymatic activities associated with recombinant NS3 protein of hepatitis C virus","volume":"72","author":"Gallinari","year":"1998","journal-title":"J. Virol."},{"key":"10.1016\/j.bioorg.2023.106408_b0445","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/emboj\/19.6.1195","article-title":"Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain","volume":"19","author":"Barbato","year":"2000","journal-title":"EMBO J."},{"key":"10.1016\/j.bioorg.2023.106408_b0450","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1021\/bi972010r","article-title":"Serine protease of hepatitis C virus expressed in insect cells as the NS3\/4A complex","volume":"37","author":"Sali","year":"1998","journal-title":"Biochemistry."},{"key":"10.1016\/j.bioorg.2023.106408_b0455","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.antiviral.2005.12.003","article-title":"Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034","volume":"70","author":"Tong","year":"2006","journal-title":"Antiviral Res."},{"key":"10.1016\/j.bioorg.2023.106408_b0460","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1039\/C9FO00733D","article-title":"Water-soluble extracts from edible mushrooms (: Agaricus bisporus) as inhibitors of hepatitis C viral replication","volume":"10","author":"Gallego","year":"2019","journal-title":"Food Funct."},{"key":"10.1016\/j.bioorg.2023.106408_b0465","doi-asserted-by":"crossref","DOI":"10.3390\/md14100190","article-title":"Different culture metabolites of the Red Sea fungus Fusarium equiseti optimize the inhibition of hepatitis C virus NS3\/4A protease (HCV PR)","volume":"14","author":"Hawas","year":"2016","journal-title":"Mar. Drugs."},{"key":"10.1016\/j.bioorg.2023.106408_b0470","first-page":"546","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"10.1016\/j.bioorg.2023.106408_b0475","first-page":"1","article-title":"Open babel","volume":"3","author":"O\u2019Boyle","year":"2011","journal-title":"J. Cheminform."},{"key":"10.1016\/j.bioorg.2023.106408_b0480","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1021\/ci800166p","article-title":"Lead finder: an approach to improve accuracy of protein-ligand docking, binding energy estimation, and virtual screening","volume":"48","author":"Stroganov","year":"2008","journal-title":"J. Chem. Inf. Model."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206823000688?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206823000688?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:43:34Z","timestamp":1758617014000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206823000688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":96,"alternative-id":["S0045206823000688"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2023.106408","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. In vitro antiviral activity evaluation against Zika and Dengue viruses","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2023.106408","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"106408"}}