HIV-1 RT Inhibitors with a Novel Mechanism of Action: NNRTIs that Compete with the Nucleotide Substrate

• Published in: Viruses Vol. 2; no. 4; pp. 880 - 899
• Main Authors: Maga, Giovanni, Radi, Marco, Gerard, Marie-Aline, Botta, Maurizio, Ennifar, Eric
• Format: Journal Article Book Review
• Language: English
• Published: Switzerland MDPI AG 01.04.2010; Molecular Diversity Preservation International (MDPI)
• Subjects: competitive inhibitors; HIV; reverse transcriptase; Review; HIV; reverse transcriptase; competitive inhibitors
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v2040880

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.