literature

HIV mutation literature information.

Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors.

PMID: 24920794 2014 Journal of virology

Abstract: Each of the G118R, Y143R, Q148R, R263K, and G140S/Q148R mutations, when introduced into SIV, impaired infectiousness and replication fitness compared to wild-type virus.

Abstract: The combination of G140S/Q148R conferred high-level resistance to both RAL and EVG (>300- and 286-fold, respectively).

2014 Update of the drug resistance mutations in HIV-1.

PMID: 25101529 2014 Topics in antiviral medicine

Discussion: N155H mutants tend to predominate early in th

Discussion: Cross-resistance studies with raltegravir- and elvitegravir-resistant viruses indicate that Q148H and G140S in combination with mutations L74I/M, E92Q, T97A, E138A/K, G140A, or N155H are associated with 5-fold to 20-fold reduced dolutegravir susceptibility and reduced virologic suppression in patients.

Discussion: Minor mutations described in the Q148H/K/R pathway include L74M plus E138A, E138K, or G140S.

Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase.

PMID: 25373632 2014 Interdisciplinary sciences, computational life sciences

Abstract: Although Elvitegravir (EVG) is a newly developed antiretrovirals drug to treat the acquired immunodeficiency syndrome (AIDS), drug resistance has already been found in clinic, such as E92Q/N155H and Q148H/G140S.

Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens.

PMID: 22994529 2013 HIV medicine

Abstract: During RAL failure, the mutation N155H was detected at different levels in three patients displaying the N155H pathway and gradually declined when the double mutant Q148H+G140S was selected in one patient.

Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase.

PMID: 23075516 2013 ACS chemical biology

Introduction: Using a panel of recombinant INs that carry the Y143R, N155H and G140S-Q148H mutations, we reported that elvitegravir (EVG, Gilead Sciences), dolutegravir (DTG, ViiV Healthcare/Shionogi) and MK-0536 (Merck & Co.) retain high efficacy against these RAL-resistant mutants.

Result: As expected from our biochemical data, the G140S-Q148H mutant caused a large increase in the EC50 values for RAL and XZ-259 to 1.7 and 6.8 muM, respectively (Table 1).

Result: However, both conformations predicted modest (2- to 8-fold) increases in IC50 against the Y143R and N155H mutants and a greater increase (15- to 225-fold) against the G140S

Factors associated with virological success with raltegravir-containing regimens and prevalence of raltegravir-resistance-associated mutations at failure in the ARCA database.

PMID: 23289841 2013 Clinical microbiology and infection

Abstract: Mutations associated with RAL failure were detected in 12/24 subjects with an integrase genotype, with the prevalence of Q148H + G140S.

Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor.

PMID: 23750093 2013 Bioinformation

Introduction: Binding orientations and favorable interactions of ligands against the wild-type (WT) and three different mutation strains; Y212R (equivalent to Y143R HIV-1 IN), N224H (equivalent to N155H HIV-1 IN) and S217H (equivalent to G140S/Q148H HIV-1 IN) of PFV IN were predicted.

Introduction: The secondary mutation at position G140 (G140S) combined with primary mutation Q148K/R/H significantly enhanced drug resistance.

Discussion: The mutation strain of G140S/

PMID: 23891838 2013 Journal of structural biology

Abstract: Obtaining crystallographic structure information on the Q148H/R, G140S/A primary and secondary mutations has been elusive.

Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics.

PMID: 24146996 2013 PloS one

Method: HIV-1 IN-DNA complexes were also constructed using the Q148H/G140S and N155H IN models, but here only DTG was docked into the active site.

Method: The Q148H/G140S HIV-1 IN model was constructed following the same approach used to build the wild-type IN model.

Method: The Q148H/G140S IN-DNA-DTG model was assembled based on the DTG-bound, PFV S217H intasome in 3S3N, with the exception of the two 3' adenylate conformations published for the PFV DNA.

Impact of resistance mutations on inhibitor binding to HIV-1 integrase.

PMID: 24205814 2013 Journal of chemical information and modeling

Abstract: An important hydrogen bond between residues 145 and 148 is present in the wild-type IN but not in the G140S/Q148H mutant, accounting for the structural and dynamical differences of the 140s' loop and ultimately impairing RAL binding in the double mutant.

Abstract: However, mutants have emerged, such as E92Q/N155H and G140S/Q148H, which confer resistance to raltegravir (RAL), the first IN strand transfer inhibitor (INSTI) approved by the FDA, and to the recently approved elvitegravir (EVG).

Abstract: In the simulation of the G140S/Q148H double mutant, we observe spontaneous dissociation

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