Abstract: The network and the structure analysis also support the hypothesis that the resistance-related E138K mutation may be a mechanism to compensate for mutations in neighbor lysine residues to maintain DNA binding.
Result: E138K co-occurs with three mutations of lysine residues, one of them in K156 (K156N).
Result: By the observed co-occurrence, E138K could also be compensating for K156N.
Result: It is also possible to see that except for Y143R and E138K, all the mutations on VG3 positions are in cluster A (Figure 6), which means they either co-occur or share co-occurring partners.
Result: Other mutations that co-occur with E138K are K215N and
Delayed linkage to HIV care among asylum seekers in Quebec, Canada.
Result: One newly diagnosed patient, who was unknowingly prescribed functional monotherapy, developed full integrase inhibitor resistance (N155H, Q148R, S147G, E138K, and E92Q mutations).
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] NNRTI-associated drug resistance mutations which included A98G, L100I, K101E/H, K103N/S, V106M, V108I, E138A/K, V179D/E Y181C, Y188L/C, G190A, H221Y, P225H, F227L, and M230L.
Figure: FC resistance was evaluated based on the contribution of the number of RPV-associated mutations (L100I, Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles.
PMID: 29635166
2018
European journal of medicinal chemistry
Conclusion: In general, a series of novel diarylnicotinamide triazole analogues were rationally designed based on structure-guided approach, synthesized and evaluated for their bioactivities against HIV-1 (IIIB, K103 N + Y181C, L100I, K103 N, E138K, Y181C, Y188L and F227L + V106A) and HIV-2 (ROD) in MT-4 cells.
Conclusion: Noteworthily, regarding the inhibitory activity against E138K, the major drug resistant mutant to the new generation HIV-1 NNRTIs, 3b8 and 3b9 with triazole linker targeting the entrance channel of NNRTIs in RT
Discovery of biphenyl-substituted diarylpyrimidines as non-nucleoside reverse transcriptase inhibitors with high potency against wild-type and mutant HIV-1.
PMID: 29353724
2018
European journal of medicinal chemistry
Abstract: Compound 4b displayed an EC50 value of 1 nM against HIV-1 IIIB, 1.3 nM against L100I, 0.84 nM against K103 N, 1.5 nM against Y181C, 11 nM against Y188L, 2 nM against E138K, 10 nM against K103 N + Y181C, and almost 110 nM against F227L + V106.
"Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the chemical space of a less explored ""hydrophobic channel""."
Abstract: Notably, Z13 also showed the most potent activity against HIV-1 mutant strains including K103N (EC50 = 10 nM), E138K (EC50 = 22 nM) and RES056 (EC50 = 0.935 muM).
Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains.
Abstract: Among them, the most promising N1-aryl-2-arylthioacetamido-benzimidazoles and N1-aryl-2-aryloxyacetamido-benzimidazoles were also tested toward a panel of single- and double-mutants strain responsible for resistance to NNRTIs, showing in vitro antiviral activity toward single mutants L100I, K103N, Y181C, Y188L and E138K.
Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes.
Method: For BIC, the presence of E138K/Q148R, G140S/Q148R or N155H/Q148R was interpreted as high level resistance.
Method: For CAB, the presence of E138A/Q148R, E138K/Q148K, E138K/Q148R, G140C/Q148R, G140S/Q148R, or Q148R/N155H was interpreted as high-level resistance.
Result: Five patients (21%) with multiple mutations ( PMID: 29346270
2018
Viruses
Introduction: In the opposite way, in vitro the presence of the R263K delayed the emergence of RAL resistance-associated mutations, whereas the simultaneous presence of either the H51Y or E138K substitutions in combination with R263K somewhat mitigated this inhibitory effect.
Introduction: Interestingly, regarding both INI currently under development, BIC and CAB, they remained active against R263K-M50I and R263K-E138K double-mutants with less than <=4-fold increase in phenotypic resistance level.
Introduction: showed that the T66I substitution emerged from a wild-type virus but also from a R263K muta
Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance.
Result: 1a) the N155H variant replaced the Q148R variant and dominated the population together with the E138K + Q148K variant.
Result: 40 days after start of raltegravir, virus with Q148R had increased to 1.7% of the population and virus with E138K + Q148K had increased to 0.5%.
Result: G140S was probably not selected because it required two nucleotide changes in this HXB2 background; G140A and E138K required just one.
Result: In Pt1, resistance developed initially through E138K + Q148K and later a second variant emerged with
HIV mutation literature information.
PMID: 
2019
Frontiers in microbiology
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