A multivariate analysis of HIV-1 protease inhibitors and resistance induced by mutation.
This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the 51 derivatives considered in this study. The best results were obtained in the case of the I84V mutant for which a high number of predictions was achieved. On this basis, this statistical approach is proposed as a reliable method for the prediction of the activity of PIs, for which the data against mutant strains have not been reported.
Almerico
Anna Maria
AM
Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo, Italy. almerico@unipa.it
Tutone
Marco
M
Lauria
Antonino
A
Diana
Patrizia
P
Barraja
Paola
P
Montalbano
Alessandra
A
Cirrincione
Girolamo
G
Dattolo
Gaetano
G
D024882:Drug Resistance, Viral / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D008954:Models, Biological; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D012984:Software; D013329:Structure-Activity Relationship
D017320:HIV Protease Inhibitors