The emergence of HIV-1 drugs resistant stains remains of pivotal interest in relation to drugs development. Non nucleoside reverse transcriptase inhibitors proven to be very effective versus HIV-1 wild type but, with the only exception of diarylpyrimidines (e.g., etravirine, 1), were featured by high-level resistance versus mutated RT. The effects of two of the most clinically relevant RT mutations (Y181C; K103N) were studied by a computational approach. This involved molecular dynamics, principal components analysis (PCA) and residue interactions networks (RINs). The methodology was applied to 1 and to Indolyl Aryl Sulphones (IASs 2 and 3), a class of potent RT inhibitors active also versus mutated RT forms. The molecular insight from this study was in accordance with the proposed mechanism of resistance for studied mutations and it might be useful in the design of novel RT inhibitors with high ligand efficacy on resistant strains.
An in-silico approach aimed to clarify the role of Y181C and K103N HIV-1 reverse transcriptase mutations versus Indole Aryl Sulphones / Massarotti, Alberto; Coluccia, Antonio. - In: JOURNAL OF MOLECULAR GRAPHICS & MODELLING. - ISSN 1093-3263. - ELETTRONICO. - 63:(2016), pp. 49-56. [10.1016/j.jmgm.2015.11.013]
An in-silico approach aimed to clarify the role of Y181C and K103N HIV-1 reverse transcriptase mutations versus Indole Aryl Sulphones
COLUCCIA, Antonio
2016
Abstract
The emergence of HIV-1 drugs resistant stains remains of pivotal interest in relation to drugs development. Non nucleoside reverse transcriptase inhibitors proven to be very effective versus HIV-1 wild type but, with the only exception of diarylpyrimidines (e.g., etravirine, 1), were featured by high-level resistance versus mutated RT. The effects of two of the most clinically relevant RT mutations (Y181C; K103N) were studied by a computational approach. This involved molecular dynamics, principal components analysis (PCA) and residue interactions networks (RINs). The methodology was applied to 1 and to Indolyl Aryl Sulphones (IASs 2 and 3), a class of potent RT inhibitors active also versus mutated RT forms. The molecular insight from this study was in accordance with the proposed mechanism of resistance for studied mutations and it might be useful in the design of novel RT inhibitors with high ligand efficacy on resistant strains.File | Dimensione | Formato | |
---|---|---|---|
Massarotti_In-silico_2016.pdf
solo gestori archivio
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
3.24 MB
Formato
Adobe PDF
|
3.24 MB | Adobe PDF | Contatta l'autore |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.