Investigation of the prevalence of resistance mutations to Sofosbuvir in the NS5B region of Hepatitis C Virus genotype 1B (HCV G1b)

• Grant number: 18/05975-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2018
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Paula Rahal
• Grantee: Bárbara Floriano Molina
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Hepatitis C is an infectious disease that affects the liver that can progress to cirrhosis, hepatocarcinoma and death. The causative agent is the Hepatitis C Virus (HCV), a positive single-stranded RNA virus that belongs to the Flaviviridae family. Due to its high mutation rate, associated with the large daily production of viruses and the lack of proofreading activityof the NS5B viral polymerase, HCV is divided into 7 different genotypes. In 2012, the first direct-acting antivirals (DAAs) Boceprevir and Telaprevir (inhibitors of the NS3/NS4A protein complex) were launched in Brazil and, in 2015, was approved the second generation of the DAAs, composed of Sofosbuvir, Daclatasvir and Simeprevir, inhibitors of, respectively, the NS5B, NS5A and NS3/NS4A proteins. Direct-acting antiviral treatments showed a better sustained virological response (SVR) and fewer side effects when compared to previous treatments based on Pegylated Interferon and Ribavirin. Nevertheless, the high genetic variability of HCV allows the appearance of point mutations on the viral genome, and in some cases these mutations can be related to an acquisition of antiviral resistance and evasion of treatment. Thus, this study aims to analyse, in patients infected by HCV genotype 1b that will be submitted to treatment with Sofosbuvir, the prevalence of mutations associated with resistance on NS5B polymerase.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

AGUIAR, BRUNA FORTE; CAMPOS, GUILHERME RODRIGUES FERNANDES; RODRIGUES, JOAO PAULO VILELA; MARQUES, NAYARA NATHIE; MOLINA, BARBARA FLORIANO; BITTAR, CINTIA; SOUZA, FERNANDA FERNANDES; MARTINELLI, ANA DE LOURDES CANDOLO; RAHAL, PAULA; PEREIRA, LEONARDO REGIS LEIRA. Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil. CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY, v. 44, n. 3, p. 329-339, JUN 2020. (18/05974-7, 18/05975-3, 16/03807-0)