Corrigendum: A novel substitution in NS5A enhances resistance of hepatitis C virus genotype 3 to daclatasvir.
Corrigendum: A novel substitution in NS5A enhances resistance of hepatitis C virus genotype 3 to daclatasvir.
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DOI：
10.1099/jgv.0.001582
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Harris M
中科院分区：
文献类型：
--
作者：
Fernandes Campos GR;Ward J;Chen S;Bittar C;Vilela Rodrigues JP;Candolo Martinelli AL;Souza FF;Leira Pereira LR;Rahal P;Harris M
丙型肝炎病毒（HCV）基因型3对直接作用的抗病毒药物（DAA），特别是靶向NS5A蛋白的药物，表现出高水平的基线和获得性耐药性。为了了解这种耐药性，我们研究了一组接受NS5A DAA、达卡他韦和核苷类似物索非布韦治疗的巴西患者。我们在治疗后复发的患者中观察到NS5A氨基酸残基98处的新取代[丝氨酸至甘氨酸（S98G）]。使用两个基因型3亚基因组复制子评估这种取代对复制适合度和对DAA的抗性的影响。S98 G对复制有适度的影响，但与先前表征的耐药相关取代（RAS）Y93 H相结合，导致达卡他韦耐药性显著增加。这一结果表明，取代的组合可能驱动高水平的DAA抗性，并为NS5A靶向DAA的作用机制提供了一些线索。
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.
DOI：
10.1099/jgv.0.001496
发表时间：
2021-01
期刊：
The Journal of general virology
影响因子：
--
作者：
Fernandes Campos GR;Ward J;Chen S;Bittar C;Vilela Rodrigues JP;Martinelli ALC;Souza FF;Pereira LRL;Rahal P;Harris M
通讯作者：
Harris M