5Result: Four ""first shell"" mutations D30N, V32I, I47V and I84V alter residues making direct contacts with DRV and SQV inhibitors."
Result: First, mutation of four (D30N, V32I, I47V and I84V) of the seven residues forming the S2/S2' subsites alters their size, shape and charge.
Result: In the PR20/SQV complex, the P2' group of SQV shifts more than 1.5 A towards the shorter I84'V to compensate for the larger S2' subsite and maintain interactions with D30N, V32I, I47V and I84V (Figure 5E).
Result: Mutation PMID: 22963370
2012
Biochemistry
Abstract: Structures of wild-type protease and two mutants (PR(V32I) and PR(I47V)) with V32I and I47V substitutions, which are common in drug resistance, reveal the gem-diol tetrahedral intermediate, the separating N- and C-terminal products, and the C-terminal product of an autoproteolytic peptide.
Abstract: The complex of mutant PR(V32I) with a single C-terminal product shows density for water molecules in the other half of the binding site, including a partial occupancy water molecule interacting with the product carboxylate end and the carbonyl oxygen of one conformation of Gly27, which suggests a potential role of Gly27 in recycling from the product complex to the ligand-free e
The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?
New trends of primary drug resistance among HIV type 1-infected men who have sex with men in Liaoning Province, China.
PMID: 21417755
2011
AIDS research and human retroviruses
Abstract: Included were V32I (0.5%), M46I (2.0%), L90M (2.0%), T215C (0.5%), and Y188L (0.5%).
Drug resistance mutations in patients infected with HIV-2 living in Spain.
PMID: 21558334
2011
The Journal of antimicrobial chemotherapy
Abstract: No major mutations associated with drug resistance in HIV-1 were recognized in 29 PR, 20 RT and 5 INT sequences from antiretroviral-naive HIV-2 individuals, although natural polymorphisms with potential effects on susceptibility to PR inhibitors were recognized at 10 positions (L10V/I, V32I, M36I, M46I, I47V, Q58E, A71V/I, G73A, V82I and L89I/V) and for nucleoside reverse transcriptase inhibitors at three positions (T69N, V75I
Loss of protease dimerization inhibition activity of darunavir is associated with the acquisition of resistance to darunavir by HIV-1.
Abstract: A highly DRV-resistant in vitro-selected HIV variant and clinical HIV strains isolated from AIDS patients failing to respond to DRV-containing antiviral regimens typically had the V32I, L33F, I54M, and I84V substitutions in common in protease.
TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors.
PMID: 21896904
2011
Antimicrobial agents and chemotherapy
Abstract: IVRS performed with r13025 in the presence of DRV required less time and resulted in more PI resistance-associated mutations (V32I, I50V, G73S, L76V, and V82I; FC in DRV EC(50) = 258).
Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score.
Discussion: V32I, I47V, L76V) was relatively low and this could have influenced the covariate selection for our score.
Synthesis of new thienyl ring containing HIV-1 protease inhibitors: promising preliminary pharmacological evaluation against recombinant HIV-1 proteases.
PMID: 20108932
2010
Journal of medicinal chemistry
Abstract: The range of activity of the two most active compounds is substantially maintained or even increased against two commonly selected mutants, under drug pressure, such as V32I and V82A.
Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study.