BACKGROUND Novel indolylarylsulfones (IASs), designed through rational structure-based molecular modelling and docking approaches, have been recently characterized as effective inhibitors of the wild-type and drug-resistant mutant HIV-1 reverse transcriptase (RT). METHODS Here, we studied the interaction of selected halo- and nitro-substituted IAS derivatives, with the RT enzyme carrying the ...

The rapid emergence of drug-resistant variants of human immunodeficiency virus, type 1 (HIV-1), has limited the efficacy of anti-acquired immune deficiency syndrome (AIDS) treatments, and new lead compounds that target novel binding sites are needed. We have determined the 3.15 A resolution crystal structure of HIV-1 reverse transcriptase (RT) complexed with dihydroxy benzoyl naphthyl hydrazone...

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs h...

OBJECTIVES To determine prevalence and predictors of antiretroviral drug resistance in newly diagnosed individuals with HIV-1 infection, using a systematic approach to avoid selection bias. METHODS Plasma samples from all persons diagnosed HIV-1 seropositive at a large London centre between April 2004 and February 2006 underwent sequencing of HIV-1 reverse transcriptase (RT) and protease gene...

OBJECTIVES The aim of the study was to determine whether mutations at RT codon 208 are associated with nucleoside RT inhibitor (NRTI) exposure, NRTI resistance patterns and HIV-1 subtype. METHODS Six thousand three hundred and fifty two genotypic resistance tests linked to a clinical database were analysed. RESULTS The prevalence of mutations at codon 208 was 6/2347 (0.3%) in treatment-naiv...

In this study the uptake and metabolism of adenosine by mitochondria has been investigated. Incubation of CEM cells mitochondria preparation with [3H] -adenosine showed substantial uptake and metabolism of adenosine. Adenosine was both anabolized to AMP, ADP and ATP, and also catabolized to inosine. The highest concentration of metabolites in extracted mitochondria was due to AMP. The mito...

Inhibition of HIV replication initially targeted viral enzymes, which are exclusively expressed by the virus and not present in the human cell. The development of reverse transcriptase (RT) inhibitors started with the discovery of antiretroviral activity of the nucleoside analog zidovudine in March 1987. Currently, six major classes of antiretroviral drugs are used for the treatment of HIV-infe...

OBJECTIVE To determine the genetic diversity of HIV-1 reverse transcriptase (RT) and protease sequences and the presence of mutations linked to antiretroviral (ARV) resistance in treatment-naive, HIV-1-infected individuals living in Mali. METHODS Ninety-eight samples from ARV drug-naive, HIV-1-infected patients were collected in one clinical centre in Bamako, Mali in 2005. RT and protease gen...