{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:54:11Z","timestamp":1790366051601,"version":"4.1.0"},"reference-count":159,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T00:00:00Z","timestamp":1446768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Selection of inhibitor-resistant viral mutants is universal for viruses that display quasi-species dynamics, and hepatitis C virus (HCV) is no exception. Here we review recent results on drug resistance in HCV, with emphasis on resistance to the newly-developed, directly-acting antiviral agents, as they are increasingly employed in the clinic. We put the experimental observations in the context of quasi-species dynamics, in particular what the genetic and phenotypic barriers to resistance mean in terms of exploration of sequence space while HCV replicates in the liver of infected patients or in cell culture. Strategies to diminish the probability of viral breakthrough during treatment are briefly outlined.<\/jats:p>","DOI":"10.3390\/v7112902","type":"journal-article","created":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T11:12:15Z","timestamp":1446808335000},"page":"5746-5766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Resistance of Hepatitis C Virus to Inhibitors: Complexity and Clinical Implications"],"prefix":"10.3390","volume":"7","author":[{"given":"Celia","family":"Perales","sequence":"first","affiliation":[{"name":"Liver Unit, Internal Medicine, Laboratory of Malalties Hep\u00e0tiques, Vall d\u2019Hebron Institut de Recerca-Hospital Universitari Vall d\u2019Hebron (VHIR-HUVH), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Biologia Molecular \u201cSevero Ochoa\u201d (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Quer","sequence":"additional","affiliation":[{"name":"Liver Unit, Internal Medicine, Laboratory of Malalties Hep\u00e0tiques, Vall d\u2019Hebron Institut de Recerca-Hospital Universitari Vall d\u2019Hebron (VHIR-HUVH), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08035 Barcelona, Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, Bellaterra 08193, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Gregori","sequence":"additional","affiliation":[{"name":"Liver Unit, Internal Medicine, Laboratory of Malalties Hep\u00e0tiques, Vall d\u2019Hebron Institut de Recerca-Hospital Universitari Vall d\u2019Hebron (VHIR-HUVH), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08035 Barcelona, Spain"},{"name":"Roche Diagnostics SL, 08174 Sant Cugat del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Esteban","sequence":"additional","affiliation":[{"name":"Liver Unit, Internal Medicine, Laboratory of Malalties Hep\u00e0tiques, Vall d\u2019Hebron Institut de Recerca-Hospital Universitari Vall d\u2019Hebron (VHIR-HUVH), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08035 Barcelona, Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, Bellaterra 08193, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Domingo","sequence":"additional","affiliation":[{"name":"Centro de Biologia Molecular \u201cSevero Ochoa\u201d (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.jmb.2010.02.005","article-title":"Unfinished stories on viral quasispecies and Darwinian views of evolution","volume":"397","author":"Mas","year":"2010","journal-title":"J. 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