HIV type-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key drugs of highly active anti-retroviral therapy (HAART) in the clinical management of AIDS/HIV infection. NNRTI-based HAART regimes effectively suppress viral reproduction, are not cytotoxic and show favourable pharmacokinetic properties. First-generation NNRTIs suffer the rapid selection of viral variants, hampering the binding of inhibitors into the reverse transcriptase (RT) non-nucleoside binding site (NNBS). Efforts to improve these first inhibitors led to the discovery of second-generation NNRTIs that proved to be effective against the drug-resistant mutant HIV-1 strains. The success of such agents launched a new season of NNRTI design and synthesis. This paper reviews the characteristics of second-generation NNRTIs, including etravirine, rilpivirine, RDEA-806, UK-453061, BIRL 355 BS, IDX 899, MK-4965 and HBY 097. In particular, the binding modes of these inhibitors into the NNBS of the HIV-1 RT and the most clinically relevant mutant RTs are analysed and discussed. ©2010 International Medical Press.

Looking for an active conformation of the future HIV type-1 non-nucleoside reverse transcriptase inhibitors / LA REGINA, Giuseppe; Coluccia, Antonio; Silvestri, Romano. - In: ANTIVIRAL CHEMISTRY & CHEMOTHERAPY. - ISSN 0956-3202. - 20:6(2010), pp. 213-237. [10.3851/imp1607]

Looking for an active conformation of the future HIV type-1 non-nucleoside reverse transcriptase inhibitors

LA REGINA, GIUSEPPE;COLUCCIA, Antonio;SILVESTRI, Romano
2010

Abstract

HIV type-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key drugs of highly active anti-retroviral therapy (HAART) in the clinical management of AIDS/HIV infection. NNRTI-based HAART regimes effectively suppress viral reproduction, are not cytotoxic and show favourable pharmacokinetic properties. First-generation NNRTIs suffer the rapid selection of viral variants, hampering the binding of inhibitors into the reverse transcriptase (RT) non-nucleoside binding site (NNBS). Efforts to improve these first inhibitors led to the discovery of second-generation NNRTIs that proved to be effective against the drug-resistant mutant HIV-1 strains. The success of such agents launched a new season of NNRTI design and synthesis. This paper reviews the characteristics of second-generation NNRTIs, including etravirine, rilpivirine, RDEA-806, UK-453061, BIRL 355 BS, IDX 899, MK-4965 and HBY 097. In particular, the binding modes of these inhibitors into the NNBS of the HIV-1 RT and the most clinically relevant mutant RTs are analysed and discussed. ©2010 International Medical Press.
2010
reverse transcriptase inhibitors; HIV-1; inhibitors NNRTIs
01 Pubblicazione su rivista::01a Articolo in rivista
Looking for an active conformation of the future HIV type-1 non-nucleoside reverse transcriptase inhibitors / LA REGINA, Giuseppe; Coluccia, Antonio; Silvestri, Romano. - In: ANTIVIRAL CHEMISTRY & CHEMOTHERAPY. - ISSN 0956-3202. - 20:6(2010), pp. 213-237. [10.3851/imp1607]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/366769
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 61
  • ???jsp.display-item.citation.isi??? ND
social impact