Evaluation of ITX 5061, a scavenger receptor B1 antagonist: resistance selection and activity in combination with other hepatitis C virus antivirals.
Evaluation of ITX 5061, a scavenger receptor B1 antagonist: resistance selection and activity in combination with other hepatitis C virus antivirals.
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DOI：
10.1093/infdis/jir802
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发表时间：
2012-02
期刊：
影响因子：
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通讯作者：
Haihong Zhu;F. Wong-Staal;Haekyung Lee;A. Syder;J. McKelvy;R. Schooley;D. Wyles
中科院分区：
文献类型：
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作者：
Haihong Zhu;F. Wong-Staal;Haekyung Lee;A. Syder;J. McKelvy;R. Schooley;D. Wyles
ITX 5061 is a scavenger receptor B1 antagonist that has entered phase 1 clinical trials in hepatitis C virus (HCV)-infected humans. We evaluated ITX 5061 in combination with interferon-α, ribavirin, and HCV protease and polymerase inhibitors in a genotype 2a infectious virus system. ITX 5061 is a potent inhibitor of HCV replication and is additive to synergistic with interferon-α, ribavirin, BILN2061, VX950, VX1, and 2'-C-methyladenosine. Resistance selection experiments were performed using a Jc1-FEO virus co-culture system and intermittent ITX 5061 exposure under neomycin selection. We identified a mutant virus with a substitution of aspartic acid for asparagine at the highly conserved position 415 in E2 (N415D). Introduction of this mutation into wild-type virus conferred high-level resistance to ITX 5061. There was no cross-resistance between ITX 5061 and HCV protease inhibitors or interferon-α. These results suggest that ITX 5061 is a promising compound for study in combination with other HCV inhibitors.
