Analysis of Hepatitis C virus genotype 3 resistance to direct acting antivirals

• Grant number: 18/04678-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2018
• End date: August 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Paula Rahal
• Grantee: Guilherme Rodrigues Fernandes Campos
• Supervisor: Mark Harris
• 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
• Institution abroad: University of Leeds, England
• Associated to the scholarship: 16/03807-0 - Study of resistance mutations to treatment with Directly Acting antivirals in patients infected with hepatitis C virus genotype 3, BP.DR

Abstract

Hepatitis C is the liver inflammation caused by the infection of Hepatitis C virus (HCV), a positive single stranded RNA virus from the Flaviviridae family. The high replication rate, associated to the lack of proof-reading activity of the viral polymerase NS5B, leads to high mutation rate in the viral genome. As a result, the virus is classified into 7 different genotypes. In Brazil, genotype 1 is the most prevalent followed by genotype 3. The most recent treatment for HCV infected patients, in Brazil, is based on the administration of three Direct Acting Antivirals (DAAs), Simeprevir, an NS3 inhibitor; Daclatasvir, an NS5A inhibitor; and Sofosbuvir, an NS5B inhibitor. This therapy presents high Sustained Virological Response (SVR) to all genotypes when compared to previous treatment. Still, genotype 3 infected patients showed to be the most difficult to treat. There are many studies showing the presence of resistance associated mutations against these DAAs, however, the majority of them are with genotype 1. Genotype 3 correspond to about 30% of HCV cases in Brazil and literature has scarce data about resistance mutations specific to this genotype. Thus, our study aims to investigate mutations in genotype 3 that potentially confers resistance to the treatment with Daclatasvir, also testing them to different NS5A direct acting antivirals.

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)

FERNANDES CAMPOS, GUILHERME RODRIGUES; WARD, JOSEPH; CHEN, SHUCHENG; BITTAR, CINTIA; VILELA RODRIGUES, JOAO PAULO; CANDOLO MARTINELLI, ANA DE LOURDES; SOUZA, FERNANDA FERNANDES; LEIRA PEREIRA, LEONARDO REGIS; RAHAL, PAULA; HARRIS, MARK. A novel substitution in NS5A enhances resistance of hepatitis C virus genotype 3 to daclatasvir (vol 102, 001496, 2021). JOURNAL OF GENERAL VIROLOGY, v. 102, n. 3, p. 1-pg., 2021-01-01. (18/04678-5, 17/22927-0, 16/03807-0)

WARD, JOSEPH C.; BOWYER, SEBASTIAN; CHEN, SHUCHENG; CAMPOS, GUILHERME RODRIGUES FERNANDES; RAMIREZ, SANTSEHARAY; BUKH, JENS; HARRIS, MARK. Insights into the unique characteristics of hepatitis C virus genotype 3 revealed by development of a robust sub-genomic DBN3a replicon. JOURNAL OF GENERAL VIROLOGY, v. 101, n. 11, p. 1182-1190, 2020. (16/03807-0, 18/04678-5)

FERNANDES CAMPOS, GUILHERME RODRIGUES; WARD, JOSEPH; CHEN, SHUCHENG; BITTAR, CINTIA; VILELA RODRIGUES, JOAO PAULO; CANDOLO MARTINELLI, ANA DE LOURDES; SOUZA, FERNANDA FERNANDES; LEIRA PEREIRA, LEONARDO REGIS; RAHAL, PAULA; HARRIS, MARK. A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir. JOURNAL OF GENERAL VIROLOGY, v. 102, n. 1, 2021. (18/04678-5, 16/03807-0)