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IDENTIFICATION AND CHARACTERIZATION OF HCV REPLICON VARIANTS WITH REDUCED SUSCEPTIBILITY TO BENZOFURANS, AND METHODS RELATED THERETO
IDENTIFICATION AND CHARACTERIZATION OF HCV REPLICON VARIANTS WITH REDUCED SUSCEPTIBILITY TO BENZOFURANS, AND METHODS RELATED THERETO
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机译:对苯并呋喃的敏感性降低的HCV复制变种的鉴定和表征及其相关方法
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摘要
The present invention provides methods of decreasing the frequency of emergence, decreasing the level of resistance, and delaying the emergence of a treatment-resistant Hepatitis C viral infection, by administering to a subject, either in combination or in series, an inhibitor of the Hepatitis C RNA-dependent RNA polymerase NS5B, e.g., a benzofuran, such as 5-cyclopropyl-2-(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide (HCV-796), and at least one additional anti-Hepatitis C agent, e.g., a ribavirin product or an immunomodulator, such as an interferon product. Additionally, the invention relates to methods of monitoring the course of treatment of a Hepatitis C viral infection, methods of monitoring and prognosing a Hepatitis C viral infection, and methods of identifying an individual with a decreased likelihood of responding to an anti-Hepatitis C viral therapy. These methods use the sequence and/or structure of the Hepatitis C RNA-dependent RNA polymerase NS5B to identify the emergence of a treatment-resistant Hepatitis C viral infection, particularly a benzofuran (e.g., HCV-796) treatment-resistant Hepatitis C viral infection.
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机译:本发明提供了通过向受试者联合或串联给予肝炎抑制剂来降低出现频率,降低耐药性水平以及延迟对治疗有抵抗力的丙型肝炎病毒感染的出现的方法。 C RNA依赖的RNA聚合酶NS5B,例如苯并呋喃,例如5-环丙基-2-(4-氟苯基)-6-[(2-羟乙基)(甲基磺酰基)氨基] -N-甲基-1-苯并呋喃-3 -羧酰胺(HCV-796)和至少一种其他抗丙型肝炎药,例如利巴韦林产品或免疫调节剂,例如干扰素产品。另外,本发明涉及监测丙型肝炎病毒感染的治疗过程的方法,监测和预后丙型肝炎病毒感染的方法,以及鉴定对抗丙型肝炎病毒应答可能性降低的个体的方法。治疗。这些方法使用丙型肝炎病毒依赖RNA的RNA聚合酶NS5B的序列和/或结构来鉴定耐药性丙型肝炎病毒感染,特别是苯并呋喃(例如HCV-796)耐药性丙型肝炎病毒感染的出现。
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