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• W2034458110 endingPage "391" @default.
• W2034458110 startingPage "382" @default.
• W2034458110 abstract "The 1-(2-hydroxyethoxymethyl)-6-(phenylthio)thymine (HEPT)-like compounds with homocyclic moieties at the N-1 of the pyrimidinedione, including the highly potent lead compound IQP-0410, inhibit HIV-1 at sub-nanomolar concentrations primarily through a typical non-nucleoside mechanism involving allosteric inhibition at the hydrophobic binding pocket of the HIV-1 RT. Like all NNRTIs, the pyrimidinediones have no activity against HIV-2 RT. The pyrimidinediones, however, also possess a second mode of action involving inhibition of virus entry at nanomolar concentrations which extends their range of action to include HIV-2. Entry inhibition occurs through recognition of a complex conformational binding site formed upon interaction of the virus with target cells, but does not involve direct inhibition of gp120-CD4 binding. In order to further explore the means by which the pyrimidinediones act, resistant strains of HIV-1 and HIV-2 were selected in cell culture and molecularly and biologically characterized. With HIV-1, three phases of resistance selection occurred which involve an initial appearance of single amino changes in the NNRTI binding pocket, followed by changes in the envelope glycoproteins gp120 and gp41, and subsequent multiple additional changes in the RT, resulting in high level resistance to IQP-0410. With HIV-2, resistance to entry inhibition was achieved with no resistance-engendering mutations detected in the HIV-2 RT. Detailed molecular and biological characterization of IQP-0410-resistant viruses was performed to define the resistance-engendering mutations present in the RT and envelope and to quantify cross-resistance to other HIV inhibitors." @default.
• W2034458110 created "2016-06-24" @default.
• W2034458110 creator A5016976631 @default.
• W2034458110 creator A5065615514 @default.
• W2034458110 creator A5088134754 @default.
• W2034458110 date "2013-11-01" @default.
• W2034458110 modified "2023-09-26" @default.
• W2034458110 title "Selection and characterization of viruses resistant to the dual acting pyrimidinedione entry and non-nucleoside reverse transcriptase inhibitor IQP-0410" @default.
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• W2034458110 doi "https://doi.org/10.1016/j.antiviral.2013.09.005" @default.
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• W2034458110 hasPublicationYear "2013" @default.
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