Natural prevalence of NS3 gene resistance-associated substitutions (RASs) in patients with chronic hepatitis C from the state of Pará/Brazil

Virus Res. 2021 Jan 15:292:198251. doi: 10.1016/j.virusres.2020.198251. Epub 2020 Nov 28.

Abstract

The resistance of hepatitis C virus (HCV) to direct-acting antiviral agents, used in chronic hepatitis C treatment, consists of a natural process resulting from resistance-associated substitutions (RASs) at specific amino acid regions. To identify and establish the natural prevalence of RASs in the NS3 gene in patients with chronic hepatitis C in the state of Pará, northern Brazil. Molecular analysis was performed on a total of 35 patients infected with HCV genotype 1, who were treatment-naive to protease inhibitors. HCV RNA was extracted from plasma and the NS3 region was amplified and submitted to DNA sequencing (Sanger). The general natural prevalence of RASs in the NS3 gene was 37.5 % (Y56F and S122T). The substitutions Y56F (34.3 %), S122T (3.1 %), V132I (15.6 %) and V170I (9.3 %) were identified. Y56F and S122T provide resistance to the protease inhibitors grazoprevir and simeprevir, respectively. All amino acid substitutions in the NS3 gene, including RASs, identified in patients from the state of Pará were present in other Brazilian studies. The natural presence of RASs in this study reflects the elevated genetic variability of HCV.

Keywords: Antiviral drug resistance; Direct acting antivirals; HCV; Protease inhibitors.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution*
  • Antiviral Agents / pharmacology
  • Brazil
  • Drug Resistance, Viral
  • Female
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepacivirus / metabolism
  • Hepatitis C, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense
  • Prospective Studies
  • Protease Inhibitors / pharmacology
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Antiviral Agents
  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • Viral Nonstructural Proteins