title: Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors.
abstract: The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.
authors: Laboratório de Biologia Molecula, Divisão Hemocentro, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista Júlio de Mesquita Filho, Botucatu, SP, Brasil.
authors: Luciana Bonome
authors: LB
authors: Zeminian
authors: Juliana Lara
authors: JL
authors: Padovani
authors: Sílvia Maria
authors: SM
authors: Corvino
authors: Giovanni Faria
authors: GF
authors: Silva
authors: Maria Inês de Moura Campos
authors: MI
authors: Pardini
authors: Rejane Maria Tommasini
authors: RM
authors: Grotto
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000097:blood / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D012367:RNA, Viral; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases