title: Resistance to nucleotide analogue inhibitors of hepatitis C virus NS5B: mechanisms and clinical relevance.
abstract: The high barrier to the development of resistance to nucleotide analogue inhibitors of the hepatitis C virus (HCV) RNA-dependent RNA polymerase is an intriguing property of this class of drugs. The S282T substitution in the viral polymerase confers resistance to 2'-C-methylated nucleotide analogues. Although this mutation can be selected in HCV replicons, it has only been identified in very few cases in the clinic. Alternative resistance pathways are likewise rarely seen in vivo. Possible underlying mechanisms that are associated with the selection and establishment of a resistant genotype are discussed in this review.
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, Quebec H3A 2B4, Canada; Department of Biochemistry, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada; Department of Medicine, Division of Experimental Medicine, McGill University, 1110 Pine Avenue West, Montreal, Quebec H3A 1A3, Canada. Electronic address: matthias.gotte@mcgill.ca.
authors.forename: Matthias
authors.initials: M
authors.lastname: Götte
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D020125:Mutation, Missense; D009711:Nucleotides / Q000494:pharmacology*; D012641:Selection, Genetic; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D009711:Nucleotides; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase