Abstract: Polymorphism mutation sites with mutation rates in the protease region higher than 60.0% were: L63A/P/S/T 89.7%, V77I 82.2%, I72E/M/K/T/V 80.4%, I93L 75.7%, and E35D 72.9%.
Result: The sites with mutation rates higher than 60.0% included: L63A/P/S/T 89.7% (96/107), among which L63P was 70.1% (75/107); V77I 82.2% (88/107); I72E/M/K/T/V 80.4% (86/107), among which I72V was 63.6% (75/107); I93L 75.7%; E35D 72.9%.
Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis.
Result: According to the IAS-USA, the mutations associated with drug resistance, with a p >10%, were L10I, M36I, I62V, L63P, I64V, A71V/T, V77I, L90M, and I93L.
Result: Although the study of mutations in this position has been limited to L63P to assess the effect of mutations that provide non-hydrophobic characteristics, alternative mechanisms could be shown by which HIV-1 PR compensates for pharmacological stressors.
Result: The L63P mutation has a compensatory effect that increases catalytic activity from 110% to 530%; when L63P is
Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling.
Introduction: The effects of the single secondary mutations, L63P, on the conformational sampling of subtype B (LAI) sequence was also investigated because it is a common natural polymorphism contained within the PRE sequence.
Method: L63P for NMR studies did not contain the K55C mutation.
Method: Buffers were adjusted to pH 9.06 for PRE and POST and pH 9.39 for L63P.
Method: Given that the L63P construct contains only one mutation compared to subtype B, assignments were made based upon previously published results.
Method: Relaxation measurements were performed on 15N L63P at 600 MHz and 700 MHz as described previously.
Method: The L63P construct was generated using site-directed mutagenesis kit (Strategene) and made w
Systematic molecular dynamics, MM-PBSA, and ab initio approaches to the saquinavir resistance mechanism in HIV-1 PR due to 11 double and multiple mutations.
PMID: 25036111
2014
The journal of physical chemistry. B
Abstract: Furthermore, it was observed that mutation accumulation may induce stabilization to SQV and to the flaps through enhanced HB interactions that lead to improved inhibition (e.g., accumulation of mutations in complexes containing L10I, G48V, L63P, I84V, or L90M single mutations).
Abstract: Herein, we extend our analysis, which includes seven double (G48V-V82A, L10I-G48V, G48V-L90M, I84V-L90M, L10I-V82A, L10I-L6
Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity.
Result: Mutations that confer major resistance in PR1, such as G48V, L63P and I84V weaken or do not present these interactions, which basically agrees with our studies here.
Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes.
PMID: 25096075
2014
The Journal of antimicrobial chemotherapy
Result: A number of protease polymorphisms were present both at baseline and time of treatment failure: N37S, P39Q, I62V, L63P, V77I and I93L.
Result: A number of polymorphisms were present in protease at both screening and failure: E35D, L63P, I72V, V77I and I93L (Table S1).
A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF.
PMID: 25108107
2014
Journal of molecular graphics & modelling
Introduction: The multidrug-resistant (MDR)-769 HIV-1 protease consists of amino acid substitutions: L10I, M36V, M46L, I54V, I62V, L63P, A71V, V82A, I84V and L90M.
Structural modifications induced by specific HIV-1 protease-compensatory mutations have an impact on the virological response to a first-line lopinavir/ritonavir-containing regimen.
PMID: 23687186
2013
The Journal of antimicrobial chemotherapy
Abstract: Specifically, the L10V + I13V + L63P + I93L cluster, related to fast virological failure, correlated with a decreased drug affinity for the enzyme in comparison with wild-type (DeltaGmut = -30.0 kcal/mol versus DeltaGwt = -42.3 kcal/mol).
Transmitted HIV drug resistance in treatment-naive Romanian patients.
Discussion: A high frequency of minor PI resistance mutations (M36I, L63P, and K20R/I) has been reported in newly diagnosed immigrants from Spain, infected with non-B subtypes.
HIV mutation literature information.
PMID: 
2014
PloS one
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