{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:41:24Z","timestamp":1791895284808,"version":"4.3.4"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Ghent University","award":["Concerted Action Grant 01G01712"],"award-info":[{"award-number":["Concerted Action Grant 01G01712"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["PIRG-GA-2009-256300"],"award-info":[{"award-number":["PIRG-GA-2009-256300"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002749","name":"Belgian Science Policy Office","doi-asserted-by":"crossref","award":["IUAP P7\/47-HEPRO-2"],"award-info":[{"award-number":["IUAP P7\/47-HEPRO-2"]}],"id":[{"id":"10.13039\/501100002749","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-13-IFEC-0002-01"],"award-info":[{"award-number":["ANR-13-IFEC-0002-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les Hepatites Virales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecules from three different families of compounds, and we identified anti-HCV activity in cell culture for six of them. Of these, we selected a compound (B5) that is currently ending clinical phase I evaluation for neurodegenerative diseases. In hepatoma cells, B5 inhibited HCV infection in a pangenotypic and dose-dependent manner, and its antiviral activity was confirmed in primary hepatocytes. B5 also inhibited infection by pseudoparticles expressing HCV envelope glycoproteins E1 and E2, and we demonstrated that it affects a postattachment stage of the entry step. Virus with resistance to B5 was selected by sequential passage in the presence of the drug, and reverse genetics experiments indicated that resistance was conferred mainly by a single mutation in the putative fusion peptide of E1 envelope glycoprotein (F291I). Furthermore, analyses of the effects of other closely related compounds on the B5-resistant mutant suggest that B5 shares a mode of action with other 4-aminoquinoline-based molecules. Finally, mice with humanized liver that were treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            In the last 4 years, HCV therapy has been profoundly improved with the approval of direct-acting antivirals in clinical practice. Nevertheless, the high costs of these drugs limit access to therapy in most countries. The present study reports the identification and characterization of a compound (B5) that inhibits HCV propagation in cell culture and is currently ending clinical phase I evaluation for neurodegenerative diseases. This molecule inhibits the HCV life cycle by blocking virus entry. Interestingly, after selection of drug-resistant virus, a resistance mutation in the putative fusion peptide of E1 envelope glycoprotein was identified, indicating that B5 could be used to further investigate the fusion mechanism. Furthermore, mice with humanized liver treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle.\n          <\/jats:p>","DOI":"10.1128\/jvi.00404-16","type":"journal-article","created":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T06:42:08Z","timestamp":1468478528000},"page":"8422-8434","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":44,"title":["Identification of a New Benzimidazole Derivative as an Antiviral against Hepatitis C Virus"],"prefix":"10.1128","volume":"90","author":[{"given":"Thibaut","family":"Vausselin","sequence":"first","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"S\u00e9ron","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Lavie","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Atef","family":"Mesalam","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Lemasson","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes, Hepatitis C Virology, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Belouzard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"F\u00e9n\u00e9ant","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Danneels","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Rouill\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Cocquerel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lander","family":"Foquet","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arielle R.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes, Hepatitis C Virology, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Czeslaw","family":"Wychowski","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Meuleman","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Melnyk","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, Inserm, CHU Lille, UMR-S 1172-JPArc-Centre de Recherche Jean-Pierre Aubert Neurosciences et Cancer, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1626-7693","authenticated-orcid":false,"given":"Jean","family":"Dubuisson","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27259"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209562"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1213651"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.03.003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1400986"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.01.004"},{"key":"e_1_3_2_8_2","first-page":"1101","volume-title":"Fields virology","author":"Lindenbach BD","year":"2007","unstructured":"Lindenbach BD, Thiel HJ, Rice CM. 2007. Flaviviridae: the viruses and their replication, p 1101\u20131152. In Knipe DM, Howley PM (ed), Fields virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-27340-7_5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6031149"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13117"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243876"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.06.031"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00024-06"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000702"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26273"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-8-163"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-009-0132-9"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/157340608785700153"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2003.07.008"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm020960r"},{"key":"e_1_3_2_22_2","unstructured":"Melnyk P Burlet S Le Fur N Delacourte A. November 2012. New heterocycle compounds and uses thereof for the prevention or treatment of diseases involving formation of amyloid plaques and\/or where a dysfunction of the APP metabolism occurs. US patent application 2012\/0283256 A1."},{"key":"e_1_3_2_23_2","unstructured":"Melnyk P LeFur N Gay M Sergeant N Bu\u00e9e L. 2 May 2016. Novel 1 4-bis(3-aminopropyl)piperazine derivative and its use. European patent 15305384.8."},{"key":"e_1_3_2_24_2","first-page":"3858","article-title":"Growth of human hepatoma cells lines with differentiated functions in chemically defined medium","volume":"42","author":"Nakabayashi H","year":"1982","unstructured":"Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J. 1982. Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res 42:3858\u20133863.","journal-title":"Cancer Res"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12094"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.06.058"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.10.6147-6160.1994"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.8.6235-6244.1999"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1268"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01190-09"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82872-0"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001866"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.08.005"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22673"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1086\/593021"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711044105"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021756"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.6.2832-2841.2006"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2004.03.009"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25501"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40094"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1326"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/cn5003013"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02460-05"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2005.12.003"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915117107"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47429-2"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00192-15"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.8.6782-6790.1999"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02053-07"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2015.04.009"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.013"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009512"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28428"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1698"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00633-11"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24171"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24692"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(02)00475-4"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00806-5"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2011.71"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70092-5"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/2011183207"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.05.002"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28111"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-65-4-791"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1021\/mp800007x"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb100322v"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00404-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00404-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:11:47Z","timestamp":1646489507000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00404-16"}},"subtitle":[],"editor":[{"given":"M. S.","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":67,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1128\/JVI.00404-16"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00404-16","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"2016-02-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}