Abstract: The most common protease mutations that developed in tipranavir-treated individuals who experienced virologic failure were L10I/V/S, I13V, L33V/I/F, M36V/I/L V82T, V82L, and I84V.
A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism.
Result: In three of the experiments we observed an A431V amino acid substitution in the NC/p1 cleavage site, combined with known resistance substitutions in protease (V32I, M46I/L, I54V, V82A/F, and I84V).
Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir.
Abstract: Saquinavir (SQV), the first antiviral HIV-1 protease (PR) inhibitor approved for AIDS therapy, has been studied in complexes with PR and the variants PR(I) (84V) and PR(V) (82A) containing the single mutations I84V and V82A that provide resistance to all the clinical inhibitors.
Interpretation of genotype and pharmacokinetics for resistance to fosamprenavir-ritonavir-based regimens in antiretroviral-experienced patients.
PMID: 17296739
2007
Antimicrobial agents and chemotherapy
Abstract: The Zephir mutation score included 12 IAS protease mutations associated with poorer virological response: L10I/F/R/V, L33F, M36I, M46I/L, I54L/M/T/V, I62V, L63P, A71I/L/V/T, G73A/C/F/T, V82A/F/S/T, I84V, L90M, and polymorphism mutations I13V, L19I, K55R, and L89M.
Molecular dynamics and free energy studies on the wild-type and double mutant HIV-1 protease complexed with amprenavir and two amprenavir-related inhibitors: mechanism for binding and drug resistance.
PMID: 17300185
2007
Journal of medicinal chemistry
Abstract: Finally, decomposition analysis of binding free energies and the further structural analysis indicate that the dominating effect of the V82F/I84V double mutation is to distort the geometry of the binding site and hence weaken the interactions of inhibitors preshaped to the wild-type binding site.
Abstract: In the current work, the binding of amprenavir to both of the wild-type and the drug-resistant V82F/I84V mutant of the HIV-1 protease was investigated by molecular dynamics (MD) simulations and was compared to those of two inhibitors in development, TMC126 and TMC114.
Abstract: The V82F/I84V double mutation is considered as the key residue mutation of the HIV-1 protease drug resistance because it c
Genotypic resistance in plasma and peripheral blood lymphocytes in a group of naive HIV-1 patients.
Abstract: Characterization of tipranavir binding to wild-type protease, active site mutants I50V and V82F/I84V, the multidrug-resistant mutant L10I/L33I/M46I/I54V/L63I/V82A/I84V/L90M, and the tipranavir in vitro-selected mutant I13V/V32L/L33F/K45I/V82L/I84V was performed by isothermal titration calorimetry and crystallography.
Tipranavir: a new protease inhibitor for the treatment of antiretroviral-experienced HIV-infected patients.
PMID: 17425479
2007
Expert opinion on pharmacotherapy
Abstract: The TPV mutation score includes L10V, I13V, K20M/R/V, L33F, E35G, M36I, K43T, M46L, I47V, I54A/M/V, Q58E, H69K, T74P, V82L/T, N83D and I84V.
HIV-1 subtype B protease and reverse transcriptase amino acid covariation.
Abstract: This work describes the X-ray crystal structures of complexes of atazanavir with two HIV-1 protease variants, namely, (i) an enzyme optimized for resistance to autolysis and oxidation, referred to as the cleavage-resistant mutant (CRM); and (ii) the M46I/V82F/I84V/L90M mutant of the CRM enzyme, which is resistant to all approved HIV-1 protease inhibitors, referred to as the inhibitor-resistant mutant.
HIV mutation literature information.
PMID: 
2007
AIDS (London, England)
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