Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism.
PMID: 25562662
2015
Journal of molecular graphics & modelling
Method: The PDB entries are: 1T3R for the WT, 2HS1 for the V32I mutant and 2HS2 for the M46L mutant structures.
Result: According to Tables 1 and 2, the binding Gibbs free energies for the binding of TMC114 with two mutants V32I and M46L at two sites (2T) are closer to the experimental results than those binding at only active site (1T).
Result: According to the RMSD average values of the three complexes, V32I-2T complex has a higher mean (1.12 A) than the WT (1.01 A) and M46L-2T mutant (0.96 A), with a respective standard deviation (SD) of 0.21, 0.16 and 0.
Result: Analyzing the frequency distribution plot for the TriCa angle G48-G49-I50 (Figure 8c), it was found that the distribution of the angle for WT-1T and M46L-2T overlaps substant
Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria.
PMID: 25582324
2015
AIDS research and human retroviruses
Result: In the PR region, one sample displayed the K43T mutation; another one had the M46L, while a third specimen had K53Y, A71V, and I85V.
Result: The CPR analysis identified the PI mutations M46L, I85V, and F53Y as well as the NRTI mutations M41L and V75M, and the NNRTI mutations K101E, K103N, and G190A as Surveillance Drug Resistance Mutations (SDRM).
Discussion: One sample harbored the
HIV-1 transmitted drug resistance and genetic diversity among patients from Piaui State, Northeast Brazil.
Abstract: Singleton mutations to protease-inhibitor/PI, nucleoside-reverse-transcriptase-inhibitor/NRTI or non-nucleoside-reverse-transcriptase-inhibitor/NNRTI predominated (8/10): PI mutations (M46L, V82F, L90M); NRTI mutations (M41L, D67N) and NNRTI mutations (K103N/S).
Epidemiological and molecular characteristics of HIV infection among money boys and general men who have sex with men in Shanghai, China.
PMID: 25653132
2015
Infection, genetics and evolution
Abstract: Two CRF01_AE subtype-infected participants (3.8%), a 50years old MB and a 24years old general MSM, harbored viruses with a M46L mutation conferring resistance to protease inhibitors (PI).
Result: Both were of CRF01_AE subtype with PI-related major mutation, M46L, which confers resistance to nelfinavir (NFV) and other protease inhibitors.
Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.
Abstract: The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, Result: Similarly, M46IL (42%; 22/52) and L90M (25%; 13/52) were the most common PI mutations.
Discussion: Overall, transmitted protease resistance mutations were identified less frequently, with M46IL and L90M being the most common.
Discussion: The M46IL is considered a primary mutation for indinavir, but is also a common secondary mutation associated with the other PIs, except for saquinavir and darunavir.
Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.
Result: M46I/L, I85V, and L90M were the four most common PI SDRMs in SSA and SSEA, and among the six most common SDRMs in all regions.
Result: M46L was not associated with a region, accounting for 21% (24 of 117), 18% (14 of 79), 10% (16 of 156), and 12% (114 of 986) of PI SDRMs in SSA, SSEA, Latin America/Caribbean, and the pooled upper-income countries, respectively (S6 Table).
Result: In all regions, the proportion of PI-treated individuals with M46L or I85V divided by the number of ARV-naive individuals with these SDRMs was much lower than the same proportion for all other commonly occurring SDRMs.
Result: The temporal increase in the odds of
Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy.
PMID: 25923117
2015
Journal of acquired immune deficiency syndromes (1999)
Abstract: In one child, the majority species contained M184V in reverse transcriptase linked to L10F, M46I/L, I54V, and V82A in PR and a triple-class drug-resistant variant with these mutations linked to the NNRTI mutation V108I.
Result: M46L could have been present at baseline given that only 1/32 genomes contained this mutation at week 96 (P = 0.457, Fisher's exact test of the proportion of sequences with M46L at baseline versus week 96 of ART).
Discussion: Age adjusted full-dose RTV can select M46I, I54V, and
Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations.
Result: Among the 44 sequences with TDR to PIs, the most common mutations were L90M (47.7%), M46L/I (33.3%), I54V/T (21.4%), and V82A (19%).
Result: It is noteworthy that several major mutations associated to high level resistance to NRTIs (K65R, L74V, Y115F, M184V and T215Y), to NNRTIs (l100I, K101E, K103N/S, V106M, Y181C, Y188L and G190A) and
The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops.
PMID: 29124158
2015
Biochemistry and biophysics reports
Method: MDR769 L33F is based on the previously studied multi-drug resistant variant 769, MDR769, which contains the mutations Q7K, L10I, M36V, M46L, I54V, I62V, L63P, A71V, V82T, I84V, L90M.
Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease.
ViMRT
HIV mutation literature information.
PMID: 
2015
Journal of molecular graphics & modelling
