Diagnostic Accuracy of Pan-Degenerate Amplification and Adaptation Assay for HIV-1 Drug Resistance Mutation Analysis in Low- and Middle-Income Countries.
PMID: 32522826
2020
Journal of clinical microbiology
Abstract: In a cross-sectional study (June 2018 to September 2019), we evaluated the diagnostic accuracy of a simple and rapid HIVDR assay (the pan-degenerate amplification and adaptation [PANDAA] assay targeting the mutations K65R, K103NS, M184VI, Y181C, and G190A) compared to Sanger sequencing and next-generation sequencing (NGS).
Abstract: PANDAA showed strong agreement with Sanger sequencing for K65R, K103NS, M184VI, and G190A (kappa > 0.85) and substantial agreement for Y181C (kappa = 0.720).
Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs.
Abstract: Especially, compound 26 exhibited the most potent activity against wild-type and a panel of single mutations (L100I, K103N, Y181C, Y188L and E138K) with an EC50 ranging from 6.02 to 23.9 nmol/L, which were comparable to those of etravirine (ETR).
Result: 4) with average distances of (Y188/P227) 4.4 +- 0.6/3.3 +- 0.6 A for WT RT, 3.9 +- 0.4/3.4 +- 0.6 A for the K103N variant, and 4.5 +- 0.7/4.7 +- 0.7 A for the K103N/Y181C mutated enzyme.
Result: All the compounds were further evaluated against a panel of clinically relevant NNRTIs-resistant single-mutant strains (L100I, PMID: 32555643
2020
PloS one
Introduction: Patients failing an NNRTI-based first-line regimen with genotypic drug resistance mutations typically present with M184V/I, K65R, and/or thymidine analogue mutations (TAMs) and K103N, V106M/A and/or Y181C as the most prevalent NRTI and NNRTI mutations, respectively.
Result: The prevalence of other major NNRTI resistance mutations (Y181CS, Y188CH, G190A and M230L) was <=8%.
Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study.
Result: The most common mutations in NNRTIs were K103N/KN (64.69%), V179D/E (23.47%) and Y181C/YC/I (14.00%), they were M184V/MV/I (36.29%), T215F/FS/TNSY (7.50%) and K219Q (5.92%) in NRTIs, and they were Q58E/QE (4.93%), L10F/LFI (0.39%) and M46L (0.39%) in PIs.
Discovery of potential dual-target prodrugs of HIV-1 reverse transcriptase and nucleocapsid protein 7.
Abstract: Here, we characterize the mode of action of N'-(2-hydroxy-benzylidene)-3,4,5-trihydroxybenzoylhydrazone (compound 13), an N-acylhydrazone derivative that inhibited viral replication (EC50 = 10 microM), while retaining full potency against the NNRTI-resistant double mutant K103N-Y181C virus.
Result: Antiviral activity and cytotoxicity of compounds 13 and 21 were determined at 5 days on MT4 cells against HIV-1 NL4.3 wt strain and HIV-1 NL4.3 carrying the K103N-Y181C double mutation, commonly selected in patients and that confers resistance to non-nucleoside RT inhibitors (NNRTIs).
Result: Both N-acylhydrazone derivatives inhibited viral replication retaining similar potency of inhibition against the PMID: 32642769
2020
The Journal of antimicrobial chemotherapy
Abstract: The four virological failures were due to three ART interruptions and one incomplete adherence (selection of Y181C RAM).
Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site.
Abstract: Additional modifications to these compounds at the 4-position, computationally designed to compensate for the Y181C mutation, do not demonstrate improved potency.
Abstract: Comparison of 2-naphthyl phenyl ethers bound to Y181C RT reveal that compounds that interact with the invariant W229 are more capable of retaining efficacy against the resistance mutation.
Abstract: Further biochemical and structural work demonstrated differences in potency against the Y181C mutation and binding mode of the compounds.
Abstract: One class of developed compounds are the 2-naphthyl phenyl ethers, showing promising efficacy against the Y181C RT mutation.
Bioisosterism-based design and enantiomeric profiling of chiral hydroxyl-substituted biphenyl-diarylpyrimidine nonnucleoside HIV-1 reverse transcriptase inhibitors.
PMID: 32712537
2020
European journal of medicinal chemistry
Abstract: Among all the chiral derivatives, (S)-(-)-12a showed the best potency with the antiviral activities against wild-type (WT) and single mutant strains (L100I, K103 N, Y181C, E138K; especially Y188L), and RT enzyme in the low nanomolar concentration range.
Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia.
Abstract: Emergence of these mutations including the NNRTI associated mutations (Y181C and Y188C) may compromise future second- and third-line regimens in the absence of routine HIVDR testing.
Abstract: There was a relatively high occurrence of other NNRTI mutations V106A (36.2%), as well as Y188C (36.2%) and Y181C (36.2%) which confer resistance to etravirine.
Discussion: The high prevalence of the Y181C and Y188C mutations has been demonstrated in earlier studies from the region including Zambia.
Discussion: The third major finding of this study was the high prevalence of the Y188CE (36.2%) and
HIV mutation literature information.
PMID: 
2020
Journal of clinical microbiology
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