Abstract: A series of heterocyclic pyrimidinedione-based HIV-1 integrase inhibitors was prepared and screened for activity against purified integrase enzyme and/or viruses modified with the following mutations within integrase: Q148R, Q148H/G140S and N155H.
Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2.
PMID: 31965175
2020
The Journal of infectious diseases
Abstract: In IN, 11 nonpolymorphic TSMs occurred in >=4 persons: Q91R, E92AQ, T97A, G140S, Y143G, Q148R, A153G, N155H, H156R, R231 5-amino acid insertions.
Structural basis of second-generation HIV integrase inhibitor action and viral resistance.
Abstract: Glutamine-148 histidine (Q148H) and glycine-140 serine (G140S) amino acid substitutions in integrase that result in clinical INSTI failure perturb optimal magnesium ion coordination in the enzyme active site.
Abstract: The expanded chemical scaffolds of second-generation compounds mediate interactions with the protein backbone that are critical for antagonizing viruses containing the Q148H and G140S mutations.
Introduction: As a start, we analyzed respective side chains in our SIVrcm Q148H/G140S intasome structure.
Introduction: Concordantly, reverting Thr138 to Glu decreased
HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study.
Abstract: The Y143R/H/C substitutions were the most prevalent, followed by the N155H, and both Q148H/K and G140S/A in the same proportion.
Table: G140S
Discussion: According to our findings, the frequency of the substitution Q148+ >=1 secondary mutation(s) (G140A/C/S, L74I or E138A/K/T) was 12%.
Discussion: On the other hand, we do not find a significant difference between the mean viral load of the subjects with DTG resistance compared to the subjects without DTG resistance (n = 22), nor with samples harbouring a G140S/A + Q148H/R/K combination (n = 3) as desc
Susceptibility to HIV-1 integrase strand transfer inhibitors (INSTIs) in highly treatment-experienced patients who failed an INSTI-based regimen.
PMID: 32450199
2020
International journal of antimicrobial agents
Abstract: The primary INSTI resistance substitutions E138A/K, G140S, Y143C/H/R, Q148H and N155H were detected in 14 of 22 samples and were associated with resistance to one or more INSTIs, with G140S+Q148H present in 11 of 22 samples.
Abstract: Two isolates contained L74M, E138K, G140S and Q148H, or L74M, T97A, S119T, E138K, G140S,
Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs.
Introduction: In vitro selection experiments indicated that substitutions in the 74 position combined with major mutations (G140A/C/S, Q148 H/K/R) and other accessory mutations (V75I, T97A) can significantly reduce susceptibility to INSTI, whereas this mutation alone has minimal impact on INSTI susceptibility or HIV-1 replication capacity.
High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.
PMID: 32105319
2020
The Journal of antimicrobial chemotherapy
Introduction: A recent report suggested that methionine at residue 74 was in closer proximity to T97 and F121 as compared with leucine at position 74 in a modelled subtype C integrase and, of note, L74F was found to contribute to high-level dolutegravir resistance when combined with major mutations G140S and Q148H.
Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains.
PMID: 32125378
2020
The Journal of antimicrobial chemotherapy
Abstract: INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively).
Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding.
Abstract: Change in free energy for the three mutants indicated different effects, while simulation analysis showed G140S to have the largest affect on protein stability and flexibility.
Abstract: Our findings suggest the G140S mutant has the strongest effect on the HIV-1C IN protein structure and Dolutegravir binding.
Abstract: This was further supported by weaker non-bonded pairwise interaction energy and binding free energy values between the drug DTG and E92Q, Y143R and G140S mutants suggesting reduced binding affinity, as indicated by interaction analysis in comparison to the WT.
Abstract: Three mutations known to be associated with Raltegravir, Elvitegravir and Dolutegravir resistance were selected; E92Q,
Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya.
PMID: 32116431
2020
Ethiopian journal of health sciences
Abstract: However, polymorphic accessory mutations associated with reduced susceptibility of integrase inhibitors were observed in low frequency; M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%), G140S/A/C (1.1%) and E157Q (0.5%).
Result: These mutations were M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%), G140S/A/C (1.1%) and E157Q (0.5%).
HIV mutation literature information.
PMID: 
2020
Bioorganic & medicinal chemistry letters
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