FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1985478802> ?p ?o ?g. }

• W1985478802 endingPage "48" @default.
• W1985478802 startingPage "41" @default.
• W1985478802 abstract "Background & Aims To delay or prevent the selection of HCV drug-resistant variants, combination therapy will be needed. Our aim was to determine the antiviral efficacy of various combinations of non-nucleoside polymerase inhibitors (NNI) (that have a different allosteric binding site) and the barrier towards resistance development of such combinations. Methods Short-term antiviral combination assays were performed in a checkerboard format. Resistance selection experiments employing HCV replicons were performed using two different protocols: (i) a short-term treatment with fixed concentrations and (ii) a long-term treatment with increasing concentrations. Results All pair-wise combinations of NNI resulted in an additive antiviral effect in short-term antiviral assays. Combination treatment of two NNIs markedly reduced or even prevented the emergence of double resistant colonies. However, double and even triple NNI-resistant variants emerged readily when relatively low starting concentrations were used in a long-term selection protocol. Genotyping confirmed the presence of the previously published resistance mutations. For some NNI, different signature mutations appeared depending on the other NNI in the particular combination. Remarkably, variants that were selected to be resistant to three different classes of NNIs [a thiophene carboxylic acid (TCA), a benzimidazole (JT-16), and a benzofuran (HCV-796)] proved resistant to yet a fourth class of NNIs (benzothiadiazines). Conclusions Double and even triple NNI-resistant HCV replicons can be readily selected with a stepwise resistance selection protocol. Depending on the particular combination, different signature mutations may arise for some NNI. Resistance to three classes of NNI resulted in resistance to yet a fourth class. To delay or prevent the selection of HCV drug-resistant variants, combination therapy will be needed. Our aim was to determine the antiviral efficacy of various combinations of non-nucleoside polymerase inhibitors (NNI) (that have a different allosteric binding site) and the barrier towards resistance development of such combinations. Short-term antiviral combination assays were performed in a checkerboard format. Resistance selection experiments employing HCV replicons were performed using two different protocols: (i) a short-term treatment with fixed concentrations and (ii) a long-term treatment with increasing concentrations. All pair-wise combinations of NNI resulted in an additive antiviral effect in short-term antiviral assays. Combination treatment of two NNIs markedly reduced or even prevented the emergence of double resistant colonies. However, double and even triple NNI-resistant variants emerged readily when relatively low starting concentrations were used in a long-term selection protocol. Genotyping confirmed the presence of the previously published resistance mutations. For some NNI, different signature mutations appeared depending on the other NNI in the particular combination. Remarkably, variants that were selected to be resistant to three different classes of NNIs [a thiophene carboxylic acid (TCA), a benzimidazole (JT-16), and a benzofuran (HCV-796)] proved resistant to yet a fourth class of NNIs (benzothiadiazines). Double and even triple NNI-resistant HCV replicons can be readily selected with a stepwise resistance selection protocol. Depending on the particular combination, different signature mutations may arise for some NNI. Resistance to three classes of NNI resulted in resistance to yet a fourth class." @default.
• W1985478802 created "2016-06-24" @default.
• W1985478802 creator A5036860979 @default.
• W1985478802 creator A5044261377 @default.
• W1985478802 creator A5052667034 @default.
• W1985478802 creator A5089010495 @default.
• W1985478802 date "2012-01-01" @default.
• W1985478802 modified "2023-09-27" @default.
• W1985478802 title "In vitro selection and characterization of HCV replicons resistant to multiple non-nucleoside polymerase inhibitors" @default.
• W1985478802 cites W1932632320 @default.
• W1985478802 cites W1995565071 @default.
• W1985478802 cites W1997809789 @default.
• W1985478802 cites W2018578396 @default.
• W1985478802 cites W2071476529 @default.
• W1985478802 cites W2091073445 @default.
• W1985478802 cites W2103185551 @default.
• W1985478802 cites W2104866417 @default.
• W1985478802 cites W2110660825 @default.
• W1985478802 cites W2127114188 @default.
• W1985478802 cites W2146554723 @default.
• W1985478802 cites W2165260654 @default.
• W1985478802 cites W2170667448 @default.
• W1985478802 cites W2170919492 @default.
• W1985478802 cites W2245153975 @default.
• W1985478802 doi "https://doi.org/10.1016/j.jhep.2011.04.016" @default.
• W1985478802 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21703175" @default.
• W1985478802 hasPublicationYear "2012" @default.
• W1985478802 type Work @default.
• W1985478802 sameAs 1985478802 @default.
• W1985478802 citedByCount "15" @default.
• W1985478802 countsByYear W19854788022012 @default.
• W1985478802 countsByYear W19854788022013 @default.
• W1985478802 countsByYear W19854788022014 @default.
• W1985478802 countsByYear W19854788022015 @default.
• W1985478802 countsByYear W19854788022017 @default.
• W1985478802 countsByYear W19854788022018 @default.
• W1985478802 crossrefType "journal-article" @default.
• W1985478802 hasAuthorship W1985478802A5036860979 @default.
• W1985478802 hasAuthorship W1985478802A5044261377 @default.
• W1985478802 hasAuthorship W1985478802A5052667034 @default.
• W1985478802 hasAuthorship W1985478802A5089010495 @default.
• W1985478802 hasConcept C104317684 @default.
• W1985478802 hasConcept C135763542 @default.
• W1985478802 hasConcept C141231307 @default.
• W1985478802 hasConcept C159047783 @default.
• W1985478802 hasConcept C18103114 @default.
• W1985478802 hasConcept C2522874641 @default.
• W1985478802 hasConcept C2777869810 @default.
• W1985478802 hasConcept C2779465607 @default.
• W1985478802 hasConcept C2780593183 @default.
• W1985478802 hasConcept C31467283 @default.
• W1985478802 hasConcept C54355233 @default.
• W1985478802 hasConcept C82381507 @default.
• W1985478802 hasConcept C86803240 @default.
• W1985478802 hasConceptScore W1985478802C104317684 @default.
• W1985478802 hasConceptScore W1985478802C135763542 @default.
• W1985478802 hasConceptScore W1985478802C141231307 @default.
• W1985478802 hasConceptScore W1985478802C159047783 @default.
• W1985478802 hasConceptScore W1985478802C18103114 @default.
• W1985478802 hasConceptScore W1985478802C2522874641 @default.
• W1985478802 hasConceptScore W1985478802C2777869810 @default.
• W1985478802 hasConceptScore W1985478802C2779465607 @default.
• W1985478802 hasConceptScore W1985478802C2780593183 @default.
• W1985478802 hasConceptScore W1985478802C31467283 @default.
• W1985478802 hasConceptScore W1985478802C54355233 @default.
• W1985478802 hasConceptScore W1985478802C82381507 @default.
• W1985478802 hasConceptScore W1985478802C86803240 @default.
• W1985478802 hasIssue "1" @default.
• W1985478802 hasLocation W19854788021 @default.
• W1985478802 hasLocation W19854788022 @default.
• W1985478802 hasOpenAccess W1985478802 @default.
• W1985478802 hasPrimaryLocation W19854788021 @default.
• W1985478802 hasRelatedWork W1996573913 @default.
• W1985478802 hasRelatedWork W2002128513 @default.
• W1985478802 hasRelatedWork W2023942967 @default.
• W1985478802 hasRelatedWork W2038282883 @default.
• W1985478802 hasRelatedWork W2083372796 @default.
• W1985478802 hasRelatedWork W2324741940 @default.
• W1985478802 hasRelatedWork W2518509642 @default.
• W1985478802 hasRelatedWork W3025124977 @default.
• W1985478802 hasRelatedWork W3130085093 @default.
• W1985478802 hasRelatedWork W4200110245 @default.
• W1985478802 hasVolume "56" @default.
• W1985478802 isParatext "false" @default.
• W1985478802 isRetracted "false" @default.
• W1985478802 magId "1985478802" @default.
• W1985478802 workType "article" @default.