Abstract: Compound 10p exhibited the best activity against wild-type HIV-1 with an EC50 (50% HIV-1 replication inhibitory concentration) value of 0.027 microM, an acceptable CC50 (50% cytotoxic concentration) value of 36.4 microM, and selectivity index of 1361, with moderate activities against the single mutants (EC50: E138K, 0.17 microM; Y181C, 0.87 microM; K103N, 0.9 microM; L100I, 1.21 microM, respectively), and an IC50 value of 0.059 microM against the RT enzyme, which was six-fold higher than nevirapine (
Conclusion: The best compound 10p exhibited EC50 values of 0.027, 0.17, 0.87, 0.90, and 1.21 microM against the WT, E138K, Y181C, K103N, and L100I variants, respectively.
HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals.
Conclusion: SDRMs (D67N and D67E) belonging to the NRTIs class were found in two subjects and
Result: K103N is a non-polymorphic mutation that induces high-level reductions in the susceptibility to Nevirapine (NVP) and Efavirenz (EFV).
Result: It was also observed that the SDRMs belonged to the NNRTIs class including K103N and V106A detected in three patients.
Result: The most common mutations were M46I and I47V for PIs, M184V for NRTIs, and K103N/S for NNRTIs (Table 6).
Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors.
Abstract: On the other hand, it was observed that those two compounds were less effective with EC50 values of 2.77 and 4.87 mumol/L for HIV-1A17 (K103N + Y181C).
Introduction: The most promising compound DB02 exhibited potent anti-HIV-1 activity against laboratory adapted strains and primary isolated strains (EC50s (concentrations inhibiting virus replication by 50%) range from 2.40 to 41.8 nmol/L), along with an improved sensitivity against K103N or Y181C than S-DABOs26.
Result: However, for HIV-1A17, a multi-drug resistant strain of NNRTIs carrying the K103N and Y181C mutations, I-11, I-12 and DB02 all showed a significantly reduced inhibitory activity with EC50 values of 2.77, 4.87 and 6.01 mumol/L.
Result: Since the new gen
Drug resistance after cessation of efavirenz-based antiretroviral treatment started in pregnancy.
PMID: 32158555
2020
Southern African journal of HIV medicine
Abstract: Thirty-five (47%) of 74 samples yielded a genotype result, and four (11%) had a major drug resistance mutation: two with K103N and two with V106M.
Result: Thirty-five (47%) of 74 samples were successfully sequenced, with 4 (11%) of 35 having a major drug resistance mutation: 2 with K103N and 2 with V106M (Table 1).
Table: K103N
Doravirine: a new non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection.
PMID: 32163527
2020
Drugs of today (Barcelona, Spain
Abstract: It has a novel resistance pathway so that it retains in vitro activity against clinically relevant NNRTI viral mutations K103N, Y181C and G190A.
Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection.
Abstract: Importantly, doravirine remains active against K103N viruses in vitro, and limited clinical evidence suggests this to be the case in patients as well.
Abstract: Since K103N is by far the most prevalent (<70%) NNRTI substitution found in clinical practice, resistance against doravirine-based antiretroviral therapies is expected to be rare, even for treatment-experienced individuals.
Introduction: Across those clinical isolates (no subtype information was provided), DOR displayed a good antiviral activity with fold changes in EC50<9 against most single mutant viruses, including A98G, E138A/G/K/Q, G190A, K101E/P, K103N/S, L100I, <
Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China.
Discussion: Discussion: G190A caused high-level resistance to NVP and intermediate resistance to EFV and could result in attenuation of the resistance that occurs with K103N alone, and G190A had a higher frequency (83.47%) of drug resistance in the HIV-1 CRF 01AE subtype in this study.
Discussion: K103N/S (41.32%) was the most frequently observed resistance mutation in NNRTIs, followed by Y181C(27.83%) and G190A(26.21%), This is a consequence of the frequent use of NNRTI-based (EFV/NVP) first-line therapy for more than a decade in China, and these results are similar to the data from low- and middle-income countries.
Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort.
Result: Of the four false-negative results, three were K103N/S (at 10.5, 11.9, and 22.4% mutant frequency) and one at G190A (at 20.59% mutant frequency).
Result: There were no IND results at K103N/S and M184V.
Discussion: K102Q/R, K103R, and K104R have not been associated with reduced susceptibility to NNRTIs, but can interfere with detection of K103N by OLA-Simple, as their presence could interfere with the DNA ligase requirement that the four nucleotides surrounding the ligation site have perfect complementarity with the target, causing an IND result.
Discussion: Probe design for K103N proved particula
Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs.
5Result: As shown in Figure 5A-C, B4 efficiently occupied the pockets of the single amino acid mutations K103N and E138K and the double mutants F227L + V106A with an approximately ""U"" conformation, which was one of the essential condition for the antiviral activity in the DAPY scaffold."
5Result: Docking of B4 with K103N + Y181C predicted that several common features (""U"" binding conformation, hydrogen bonds, and pi-pi stacking interactions) would be lost, which might contribute
Abstract: Moreover, these two compounds had EC50 values of 0.06 and 0.08 muM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 muM).
Characterization of viral rebounds on dual etravirine/raltegravir maintenance therapy (ANRS-163 ETRAL trial).
PMID: 32259255
2020
The Journal of antimicrobial chemotherapy
Abstract: For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline.
HIV mutation literature information.
PMID: 
2020
Molecules (Basel, Switzerland)
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