A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir.
J Gen Virol
; 102(1)2021 01.
Article
en En
| MEDLINE
| ID: mdl-33141008
ABSTRACT
Hepatitis C virus (HCV) genotype 3 presents a high level of both baseline and acquired resistance to direct-acting antivirals (DAAs), particularly those targeting the NS5A protein. To understand this resistance we studied a cohort of Brazilian patients treated with the NS5A DAA, daclatasvir and the nucleoside analogue, sofosbuvir. We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. The effect of this substitution on both replication fitness and resistance to DAAs was evaluated using two genotype 3 subgenomic replicons. S98G had a modest effect on replication, but in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance. This result suggests that combinations of substitutions may drive a high level of DAA resistance and provide some clues to the mechanism of action of the NS5A-targeting DAAs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Pirrolidinas
/
Valina
/
Carbamatos
/
Proteínas no Estructurales Virales
/
Hepacivirus
/
Farmacorresistencia Viral
/
Imidazoles
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Humans
País/Región como asunto:
America do sul
/
Brasil
Idioma:
En
Revista:
J Gen Virol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Brasil