title: HIV-1 RT Inhibitors with a Novel Mechanism of Action: NNRTIs that Compete with the Nucleotide Substrate.
abstract: 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.
authors: Istituto di Genetica Molecolare, IGM-CNR, Via Abiategrasso 207, 27100 Pavia, Italy.
authors: Giovanni
authors: G
authors: Maga
authors: Dipartimento Farmaco Chimico Tecnologico, University of Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
authors: Marco
authors: M
authors: Radi
authors: Architecture et Réactivité des ARN, Université de Strasbourg, CNRS, 15 rue René Descartes, F-67084 Strasbourg, France.
authors: Marie-Aline
authors: MA
authors: Gerard
authors: Dipartimento Farmaco Chimico Tecnologico, University of Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
authors: Maurizio
authors: M
authors: Botta
authors: Architecture et Réactivité des ARN, Université de Strasbourg, CNRS, 15 rue René Descartes, F-67084 Strasbourg, France.
authors: Eric
authors: E
authors: Ennifar