literature

Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease.

PMID: 26695135 2015 BMC bioinformatics

Introduction: L23I, D30N, E35G, M46I/L/V, G48V, I54L, G73S/T/C/A, T74S, V82A/F/S/T, I84V, N88D/S and L90M are other mutations correlated to NFV resistance.

Introduction: The other mutations which were co-occurring with DBM and TPM included major mutations like- M46IL, I54MV, I84V, L90M, N88S, V32I,

PMID: 26715861 2015 HIV/AIDS (Auckland, N.Z.)

Result: The 22 cases experiencing virologic failure presented with the following DRMs: M46I, F53LY, I54LTV, G73ST, L76V, V82AT, I84V, I185V, N88D, and L90M for PIs; L100I, K103NS, V179F Y181C, G190AS, V106A, K103N, and P225H for NNRTIs; and

HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

PMID: 26717411 2015 PloS one

Result: The most common major PI DRMs were V82A, I76V, I84V and L47A.

Table: I84V

Discussion: Our analysis suggests that the four mutations V82A, L76V, I84V, and I47A would have a sensitivity approaching 90% for detecting intermediate or high-level LPV resistance and that I50L and N88S are the most common major PI-associated DRMs to develop in individuals with VF and intermediate or high-level ATV resistance on an initial ATV/r-associated regimen.

Dimerization of HIV-1 protease occurs through two steps relating to the mechanism of protease dimerization inhibition by darunavir.

PMID: 25092296 2014 Proc Natl Acad Sci U S A

Abstract: Notably, DRV failed to bind to mutant PR containing four amino acid substitutions (V32I, L33F, I54M, and I84V) that confer resistance to DRV on HIV-1.

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

Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps.

PMID: 24738918 2014 ACS chemical biology

Method: The PRP51 construct contains 14 mutations (L10I, I15V, K20R, L24I, V32I, L33F, M36I, M46L, I54M, L63P, K70Q, V82I, I84V, and L89M) plus three other mutations Q7K to minimize autoproteolysis and C67A and C95A to prevent cysteine-induced aggregation.

Result: Four mutations associated with drug resistance, V32I,

PMID: 24681625 2014 PloS one

Resu

Result: Four amino acid substitutions occurred at naturally polymorphic HIV-2 positions, but were considered in our analysis because they were previously reported as resistance associated mutations in integrase sequences from RAL-treated HIV-2 patients: I84V (n = 4), A153G (n = 3), H157N/S/R (n = 1) and S163D (n = 1).

Result: In these patients, we further observed two amino acid changes that were previously described as secondary mutations in the HIV-2 IN, I84V and S163G/D, and two polymorphisms at positions previously associated with HIV-2 INSTIs resistance: H51Q, I175L/V.

Genotypic resistance profiles of HIV-2-treated patients in West Africa.

PMID: 24583671 2014 AIDS (London, England)

Method: Among the protease inhibitor resistance mutations, the I50V, I54M, and I84V were associated with resistance to darunavir.

Method: In this study, HIV-2 resistance mutations were identified using the list generated by the 'Collaborative HIV and Anti-HIV Drug Resistance Network', leading to the following mutations in reverse transcriptase - K65R, D67G/N, N69S/T, K70N/R, L74V, V111I, Y115F, M184I/V, Q151M, S215A/C/F/L/Y,

The impact of active site mutations of South African HIV PR on drug resistance: Insight from molecular dynamics simulations, binding free energy and per-residue footprints.

PMID: 24267738 2014 Chemical biology & drug design

Abstract: Against the V82F/I84V variant, saquinavir, indinavir, and nelfinavir lose remarkable entropic contributions relative to both wild-type and V82A C-SA HIV PRs.

Abstract: Molecular dynamics simulations and binding free energy calculations were used to provide an understanding of the impact of active site drug-resistant mutations of the South African HIV protease subtype C (C-SA HIV PR), V82A and V82F/I84V on drug resistance.

Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis.

PMID: 24629078 2014 BMC bioinformatics

Result: We modelled the proteins with unusual mutations (L5F, D29V, L63G, L63R, P79L and T91V), natural polymorphisms (L63H andL63S), and drug-resistant mutant PRs with single mutations or patterns of mutations (D30N, V32I, M36I, M46I, I47V, G48V, I50V, I50L, I54M, Q58E, T74P,

Table: I84V