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Despite the recent approval of specific drugs targeting HCV replication to be used in combination with alpha interferon (IFN-\u03b1) and ribavirin, there is still an urgent need for pangenotypic, interferon-free therapies to fight this genetically diverse group of viruses. In this study, we used an unbiased screening cell culture assay to interrogate a chemical library of compounds approved for clinical use in humans. This system enables identifying nontoxic antiviral compounds targeting every aspect of the viral life cycle, be the target viral or cellular. The aim of this study was to identify drugs approved for other therapeutic applications in humans that could be effective components of combination therapies against HCV. As a result of this analysis, we identified 12 compounds with antiviral activity in cell culture, some of which had previously been identified as HCV inhibitors with antiviral activity in cell culture and had been shown to be effective in patients. We selected two novel HCV antivirals, hydroxyzine and benztropine, to characterize them by determining their specificity and genotype spectrum as well as by defining the step of the replication cycle targeted by these compounds. We found that both compounds effectively inhibited viral entry at a postbinding step of genotypes 1, 2, 3, and 4 without affecting entry of other viruses.<\/jats:p>","DOI":"10.1128\/aac.02619-14","type":"journal-article","created":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T23:12:41Z","timestamp":1396912361000},"page":"3451-3460","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Selective Inhibition of Hepatitis C Virus Infection by Hydroxyzine and Benztropine"],"prefix":"10.1128","volume":"58","author":[{"given":"Lidia","family":"Mingorance","sequence":"first","affiliation":[{"name":"Centro Nacional De Biotecnolog\u00eda-Consejo Superior de Investigaciones Cient\u00edficas (CNB-CSIC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Friesland","sequence":"additional","affiliation":[{"name":"Centro Nacional De Biotecnolog\u00eda-Consejo Superior de Investigaciones Cient\u00edficas (CNB-CSIC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mairene","family":"Coto-Llerena","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sof\u00eda","family":"P\u00e9rez-del-Pulgar","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loreto","family":"Boix","sequence":"additional","affiliation":[{"name":"Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Cl\u00ednic, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Manuel","family":"L\u00f3pez-Oliva","sequence":"additional","affiliation":[{"name":"Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Cl\u00ednic, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Bruix","sequence":"additional","affiliation":[{"name":"Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Cl\u00ednic, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Forns","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Gastaminza","sequence":"additional","affiliation":[{"name":"Centro Nacional De Biotecnolog\u00eda-Consejo Superior de Investigaciones Cient\u00edficas (CNB-CSIC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2012.09.009"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.1.110304.100230"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26744"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.11.94"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-405880-4.00005-6"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2011.12.007"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.4.1734-1741.2006"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3248"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3046"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12173"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201303131"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912966107"},{"key":"e_1_3_2_14_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":"NakabayashiHTaketaKMiyanoKYamaneTSatoJ. 1982. 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