Torsional flexibility of undecorated catechol diether compound as potent NNRTI targeting HIV-1 reverse transcriptase.
PMID: 30445408
2019
Journal of molecular graphics & modelling
Abstract: In this study, torsional flexibility of an undecorated catechol diether compound in the binding pocket of wild type and mutants (Y181C and K103N/Y181C) HIV-1 RT is investigated by using QM/MM calculations.
A comparison between two dolutegravir-based two-drug regimens as switch strategies in a multicentre cohort of HIV-1-infected patients.
Abstract: In the RPV group, during 371.0 PYFU, there were 5 VF (1 developed non-nucleoside reverse transcriptase inhibitor mutations Y181C and E138Q) and 13 TD.
Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population.
Result: Figure 5 contains a time-scaled Bayesian phylogenetic tree that illustrates in red the likely origin of the cluster of 12 viruses containing the NNRTI DRM Y181C plus the PI DRM L90M.
Result: The mutations K103N/S, Y181C, Y188L, and G190A accounted for 88.5% of the 348 NNRTI SDRMs.
Figure: One individual (PID 50) was also primarily infected with this virus as a 2002 sequence obtained prior to therapy contained Y181C + L90M (indicated in red with an open triangle) and later developed PMID: 30525601
2019
Journal of medicinal chemistry
1Abstract: The various alpha-methoxy DABO series (12-14) present different SAR at the dihalo benzyl substitution, with the most potent compounds (12d,e and 13c) showing similar (picomolar/nanomolar) anti-HIV-1 potency as the corresponding alpha-methyl analogues against wt HIV-1, and 10-100-fold increased potency (up to low nanomolar) against clinically relevant K103N, Y181C, Y188L, IRLL98, and K103N+Y181C HIV-1 mutant strains, highlighting the importance of the alpha-methoxy substitution to provide highly efficient DABOs as ""second generation"" NNRTIs."
Pretreatment HIV Drug Resistance and Virologic Outcomes to First-Line Antiretroviral Therapy in Peru.
PMID: 30560685
2019
AIDS research and human retroviruses
Abstract: Blood specimens from ARV-naive individuals were assessed for PDR to NNRTI-based ART by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant within an individual's HIV quasispecies at reverse transcriptase codons M41L, K65R, K103N, Y181C, M184V, and G190A, and by Sanger consensus sequencing (CS).
Design, synthesis and biological evaluation of novel acetamide-substituted doravirine and its prodrugs as potent HIV-1 NNRTIs.
Discussion: A competitive relationship among drug-resistant strains during long-term antiviral treatment (especially with NNRTIs) exists due to the presence of Y181C/I/V and K103 N/R/S, which affect the binding of NNRTIs to the active sites of the enzymes.
Discussion: In this study, the occurrence rates for K103 N/R/S, G190A, and V106A were higher than that for Y181C/I/V; however, after a long period, the Y181C/I/V and K103 N/R/S mutations showed a greater prevalence.
Discussion: Previous studies have performed adaptive sequencing of subjects receiving
Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties.
PMID: 30624934
2019
Journal of medicinal chemistry
Conclusion: Especially, 13c2 and 13c4 proved to be the exceptionally potent inhibitors, exhibiting EC50 values of 0.9-7.0 nM against single NNRTI-resistant strains L100I, K103N, Y181C, Y188L, and E138K in MT-4 cells and bringing approximately 1.3- to 3.6 fold improvement in potency compared with ETV (EC50 = 3.3-20.4 nM).
Result: As noted above, 13c2 can inhibit single (L100I, K103N, Y181C, Y188L, E138K) and double (F227+V106A) mutated HIV-RT variants (see Figure S3 for the location of these mutations).
Result: Five mutations
High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014.
PMID: 30640198
2019
The Pediatric infectious disease journal
Abstract: The most frequent mutations were K103N/S (48.0%), M184V (37.5%), G190A/S (15.1%), and Y181C/G/V (14.1%).
Result: The most frequent mutations observed were K103N/S (48.0%), M184V (37.5%), G190A/S/E/Q/R (15.1%), and Y181C/G/V (13.8%) (Table 1).
Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance.
PMID: 30648124
2019
Open forum infectious diseases
Conclusion: At that time, resistance testing showed NRTI (M184V, T69D, T215S, D67N, K219Q), NNRTI (Y181C, Y188L, H221Y) and PI (L10I, D30N, K20T, L33F, K43T, N88D) resistance, with PI resistance to nelfinavir.
HIV mutation literature information.
PMID: 
2019
Journal of molecular graphics & modelling
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