Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing.
PMID: 31434039
2019
European journal of medicinal chemistry
Abstract: Furthermore, some compounds maintained excellent activity against various single HIV-1 mutants (L100I, K103 N, E138K, Y181C) as well as one double mutant (F227L/V106A) with EC50 values in low-micromolar concentration ranges.
Abstract: Notably, 34 displayed outstanding potency against F227L/V106A (EC50 = 0.094 muM), and also showed exceptional activity against E138K (EC50 = 0.014 muM), L100I (EC50 = 0.011 muM) and K103 N (EC50 = 0.025 muM).
Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.
PMID: 31430369
2019
The Journal of antimicrobial chemotherapy
Method: Primary NNRTI-R substitutions were L100I, K101E/P, K103N/S, V106M/A, V108I, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188C/H/L, G190A/E/Q/S, H221Y, P225H, F227C and M230L/I in RT.
Result: NNRTI-R substitutions were observed in 23% (124/543) of participants; the most frequently detected substitutions w
Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study.
Abstract: Specifically, compound 30, which had the highest selectivity index (SI = 16094) and the best anti-reverse transcriptase ability (IC50 = 39 nM), displayed marked inhibitory activity (EC50 = 13.5, 9.4, 17.0, 52.0, and 58.2 nM) against WT, K103N, E138K, L100I, Y181C mutants and moderate activity against double mutants.
Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs.
Introduction: Compound 13 is similar to RPV in terms of its therapeutic index and its antiretroviral efficacy against a panel of HIV-1 mutants containing RT mutations, including L100I, K103N, V106A, E138K, Y181C, Y188L, H221Y, and K103N/Y181C.
Introduction: In those trials, the viruses in participants who failed RPV-containing therapies had the RT mutations L100I, K101E, K103N, V108I, E138K/R, Y1
Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens.
PMID: 30863788
2019
Open forum infectious diseases
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
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 (L100I, Y181C, Y188L, F227L, and V106) are located in the hydrophobic pocket that accommodates the benzonitrile and benzamide moieties of the ligand.
Result: In the case of L100I, Y181C, Y188L, and E138K, 13c2, 13c3, and 13c4 provided single-digit nanom
"Discovery of Novel Diarylpyrimidine Derivatives as Potent HIV-1 NNRTIs Targeting the ""NNRTI Adjacent"" Binding Site."
Abstract: Especially, 20 showed marked antiviral activity, which was 1.5-fold greater against WT and 1.5- to 3-fold greater against L100I, K103N, Y181C, Y188L, and E138K when compared with ETV.
Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus.
PMID: 29635166
2018
European journal of medicinal chemistry
Method: HIV-1 (IIIB, K103 N/Y181C (RES056), F227L/V106A, L100I, K103 N, E138K, Y181C, and Y188L) or HIV-2 (ROD) stock (50 muL at 100-300 CCID50) (50% cell culture infectious dose) or culture medium was added to either the infected or mock-infected wells of the microtiter tray.
Result: All six compounds showed same sensitivity order against the six mutant viruses as follows: Y188L (least sensitive to these compounds) < L100I < F227L + V106A < K103 N < Y181L < E138K (
Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa.
Method: Plasma samples contained a median of 3 [Q1-Q3: 2-4] Figure: FC resistance was evaluated based on the contribution of the number of RPV-associated mutations (L100I, K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) per sample with and without K103N.
Discussion: Other studies have reported an association of RPV resistance with K103N combined with other NNRTI resistance mutations, especially L100I, in clinical samples.
HIV mutation literature information.
PMID: 
2019
European journal of medicinal chemistry
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