Resistance profiles of (+)2'-deoxy-3'-oxa-4'-thiocytidine and (-)2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine.

N Richard, H Salomon, M Oliveira, R Rando, M A Wainberg
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引用次数: 1

Abstract

Resistant variants were selected in vitro against two novel nucleoside analogues, (+) dOTC and (-) dOTFC using the HIV-1 molecular clone HXB2D. The variants obtained displayed 6.5-fold and 10-fold resistance to these compounds, respectively. Cloning and sequencing of the RT genes of the selected viruses identified two mutations, M184I for (+) dOTC and M184V for (-) dOTFC. Results with mutated recombinant clones of HXB2D confirmed the importance of these mutations in MT-4 cells. The resistance profiles of clinical samples with wild-type or 3TC-resistant phenotypes were also studied; low to moderate levels of cross-resistance were observed against the novel compounds.

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(+)2'-脱氧-3'-氧-4'-硫代胞苷和(-)2'-脱氧-3'-氧-4'-硫-5-氟代胞苷的抗性谱。
利用HIV-1分子克隆HXB2D,在体外筛选了两种新型核苷类似物(+)dOTC和(-)dOTFC的耐药变体。获得的变异对这些化合物的抗性分别为6.5倍和10倍。对所选病毒的RT基因进行克隆和测序,鉴定出(+)dOTC的M184I和(-)dOTFC的M184V两个突变。HXB2D突变重组克隆的结果证实了这些突变在MT-4细胞中的重要性。研究了野生型和3tc耐药表型临床样品的耐药谱;观察到对新化合物的低至中等水平的交叉抗性。
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