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Looking at the Molecular Target of NS5A Inhibitors throughout a Population Highly Affected with Hepatitis C Virus

dc.contributor.authorRamos, Diogo
dc.contributor.authorPinto, Miguel
dc.contributor.authorSousa Coutinho, Rodrigo
dc.contributor.authorSilva, Carolina
dc.contributor.authorQuina, Miriam
dc.contributor.authorGomes, João Paulo
dc.contributor.authorPádua, Elizabeth
dc.date.accessioned2024-02-12T15:15:46Z
dc.date.available2024-02-12T15:15:46Z
dc.date.issued2023-05-24
dc.description.abstractHepatitis C virus (HCV) is associated with liver damage and an increased progression rate to cirrhosis and hepatocellular carcinoma. In Portugal, it is prevalent in vulnerable populations such as injection drug users (IDU). HCV is characterized by a high intra-host variability, and the selecting driving forces could select variants containing resistance-associated substitutions (RAS) that reduce treatment effectiveness. The main goal of this study was to analyze the sequence variation of NS5A in treatment-naïve IDU. The epidemiological and clinical status of hepatitis C were analyzed, and samples were sequenced by Sanger and Next-Generation sequencing (NGS) to assess RAS and confirm HCV subtypes. Phylogenetic classification was concordant: 1a, 52.4%; 1b, 10.7%; 3a, 20.2%; 4a, 8.3%; 4d, 7.1%; and one 2k/1b recombinant. A 1a/3a mixed infection was detected by NGS. RAS were found in 34.5% (29/84) of samples using Sanger sequencing, while in 42.9% (36/84) using NGS. In sequences from subtypes 1a and 1b, RAS K24R, M28V, Q30H/R, H58D/P/Q/R, and RAS L31M and P58S were detected, respectively. In subtype 3a, RAS A30S/T, Y93H and polymorphisms in position 62 were identified. Additionally, RAS P58L was detected in genotype 4. The strategy used for the molecular survey of baseline HCV resistance is of particular importance to achieve treatment effectiveness and contribute to the elimination of hepatitis C.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPathogens. 2023 May 24;12(6):754. doi: 10.3390/pathogens12060754pt_PT
dc.identifier.doi10.3390/pathogens12060754pt_PT
dc.identifier.issn2076-0817
dc.identifier.urihttp://hdl.handle.net/10400.18/9086
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2076-0817/12/6/754pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectHepatitis C Viruspt_PT
dc.subjectHCVpt_PT
dc.subjectNGSpt_PT
dc.subjectNS5Apt_PT
dc.subjectPortugalpt_PT
dc.subjectSangerpt_PT
dc.subjectNext-Generation Sequencingpt_PT
dc.subjectDrug Userspt_PT
dc.subjectResistance-associated Substitutionspt_PT
dc.subjectInfecções Sexualmente Transmissíveispt_PT
dc.titleLooking at the Molecular Target of NS5A Inhibitors throughout a Population Highly Affected with Hepatitis C Viruspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue6pt_PT
oaire.citation.startPage754pt_PT
oaire.citation.titlePathogenspt_PT
oaire.citation.volume12pt_PT
rcaap.embargofctAcesso de acordo com a política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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