Inhibition of HIV-1 reverse transcription: basic principles of drug action and resistance.
Inhibition of HIV-1 reverse transcription: basic principles of drug action and resistance.
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DOI：
10.1586/14789072.2.5.707
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发表时间：
2004-10-01
影响因子：
5.7
通讯作者：
Gotte, Matthias
中科院分区：
文献类型：
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作者：
Gotte, Matthias
HIV 1型逆转录酶的核苷和非核苷类似物抑制剂目前在临床上用于治疗这种逆转录病毒感染。在它们的细胞内活化后，核苷类似物充当链终止剂，而非核苷类似物逆转录酶抑制剂结合到紧邻活性位点的疏水口袋并抑制催化步骤。属于两种不同药物类别的化合物经常组合施用以利用药物作用的不同机制。然而，耐药性的发展可能发生在持续、残留病毒复制的条件下，这是治疗失败的主要原因。本文综述了不同的抑制剂和耐药基因突变之间的相互作用，在联合治疗的背景下，靶向逆转录酶的药物。重点放在生化机制和未来方法的发展。
Nucleoside and non-nucleoside analog inhibitors of HIV Type 1 reverse transcriptase are currently used in the clinic to treat infection with this retrovirus. Following their intracellular activation, nucleoside analogs act as chain terminators, while non-nucleoside analog reverse transcriptase inhibitors bind to a hydrophobic pocket in close proximity to the active site and inhibit the catalytic step. Compounds that belong to the two different classes of drugs are frequently administered in combination to take advantage of the different mechanisms of drug action. However, the development of drug resistance may occur under conditions of continued, residual viral replication, which is a major cause of treatment failure. This review addresses the interaction between different inhibitors and resistance-conferring mutations in the context of combination therapy with drugs that target the reverse transcriptase enzyme. Focus is placed on biochemical mechanisms and the development of future approaches.