Discussion: The mutation strain of G140S/Q148H in HIV-1 IN has > 150-fold reduced susceptibility to raltegravir .
Discussion: The predicted binding modes of both M522 and M532 with the S209/S217H mutant (equivalent to G140S/Q148H HIV-1 IN) are displayed in Figure 3D.
Discussion: This is different in the case of M522 and M532, Although the mutation of S217H (corresponding to G140S/Q148H of HIV-1 IN) disturbed the inhibitor binding mode, it is likely that both compounds were capable to preserve the main interactions with Mg2+ ions, the contacting amino acids and viral DNA.
In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir.
PMID: 23798668
2013
The Journal of antimicrobial chemotherapy
Abstract: Only Q148H/R variants had a reduced level of susceptibility (FC 5.48-18.64).
Reduced HIV-1 integrase flexibility as a mechanism for raltegravir resistance.
Abstract: Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir.
Method: <
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.
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
Plasma raltegravir exposure influences the antiviral activity and selection of resistance mutations.
PMID: 21457126
2012
AIDS research and human retroviruses
Abstract: Integrase sequences could be obtained for 89 (84%), of whom 30 (33.7%) depicted primary RAL resistance mutations (15 N155H, eight Q148H/R, three Y143R, one E92Q, and three more than one of them).
Molecular dynamics approaches estimate the binding energy of HIV-1 integrase inhibitors and correlate with in vitro activity.
PMID: 22037850
2012
Antimicrobial agents and chemotherapy
Abstract: Four well-characterized compounds (raltegravir, elvitegravir, MK-0536, and dolutegravir) were used as a training set, and the data for their in vitro activity against the Y143R, N155H, and G140S/Q148H mutants were used in addition to the wild-type (WT) IN data.
PMID: 22107736
2012
Chemical biology & drug design
Abstract: A representative inhibitor (5e) retained most of its inhibitory potency against the three major raltegravir-resistant IN mutant enzymes, G140S/Q148H, Y143R, and N155H.
Abstract: In antiviral assays employing viral vectors coding these IN mutants, compound 5e was approximately 200- and 20-fold less affected than raltegravir against the G140S/Q148H and Y143R mutations, respectively.
Abstract: Thus, our new compounds represent a novel structural class that may be further developed to overcome resistance to raltegravir, particularly in the case of the G140S/Q148H mutations.
Method: T
Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing.
PMID: 22238474
2012
The Journal of infectious diseases
Abstract: At UDPS, not all resistant variants appearing early during treatment evolved as major populations during failure; only specific resistance pathways (Y143R-Q148H/R-N155H) associated with an increased rate of fitness and phenotypic resistance were selected.
Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo.
Abstract: Evaluation of molecular clones isolated from different time points demonstrated that Y143R and Q148H variants exhibited larger reductions in RAL susceptibility and higher IN-mediated replication capacity (RC) than N155H variants within the same subject.
Abstract: Patient viruses containing Y143R, Q148R, or Q148H mutations consistently exhibited larger reductions in RAL susceptibility than patient viruses containing N155H mutations.
Abstract: Sequential analyses of virus populations from three subjects revealed temporal shifts in subpopulations representing N155H, Y143R, or Q148H escape pa
HIV mutation literature information.
PMID: 
2013
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