Istituto di Genetica Molecolare, IGM-CNR, Via Abiategrasso 207, 27100 Pavia, Italy.
Dipartimento Farmaco Chimico Tecnologico, University of Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
Viruses. 2010 Apr;2(4):880-899. doi: 10.3390/v2040880. Epub 2010 Mar 30.
HIV-1 reverse transcriptase (RT) inhibitors currently used in antiretroviral therapy can be divided into two classes: (i) nucleoside analog RT inhibitors (NRTIs), which compete with natural nucleoside substrates and act as terminators of proviral DNA synthesis, and (ii) non-nucleoside RT inhibitors (NNRTIs), which bind to a hydrophobic pocket close to the RT active site. In spite of the efficiency of NRTIs and NNRTIs, the rapid emergence of multidrug-resistant mutations requires the development of new RT inhibitors with an alternative mechanism of action. Recently, several studies reported the discovery of novel non-nucleoside inhibitors with a distinct mechanism of action. Unlike classical NNRTIs, they compete with the nucleotide substrate, thus forming a new class of RT inhibitors: nucleotide-competing RT inhibitors (NcRTIs). In this review, we discuss current progress in the understanding of the peculiar behavior of these compounds.
HIV-1 逆转录酶 (RT) 抑制剂目前在抗逆转录病毒治疗中可分为两类：(i) 核苷类似物逆转录酶抑制剂 (NRTIs)，与天然核苷底物竞争，并作为前病毒 DNA 合成的终止子；(ii) 非核苷逆转录酶抑制剂 (NNRTIs)，与 RT 活性位点附近的疏水口袋结合。尽管 NRTIs 和 NNRTIs 具有高效性，但多药耐药突变的迅速出现需要开发具有替代作用机制的新型 RT 抑制剂。最近，有几项研究报告了具有独特作用机制的新型非核苷抑制剂的发现。与经典的 NNRTIs 不同，它们与核苷酸底物竞争，从而形成一类新的 RT 抑制剂：核苷酸竞争 RT 抑制剂 (NcRTIs)。在这篇综述中，我们讨论了目前对这些化合物特殊行为的理解进展。
