Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors.
Abstract: In the case of the second generation compounds efavirenz with Tyr181Cys RT and UC-781 with Tyr188Cys RT there are only small rearrangements of either inhibitor within the binding site compared to wild-type RT and also for the first generation compounds TNK-651, PETT-2 and nevirapine with Tyr181Cys RT.
Abstract: The main contribution to drug resistance for Tyr181Cys and Tyr188Cys RT mutations is the loss of aromatic ring stacking interactions for first generation compounds, providing a simple explanation for the resilience of second generation NNRTIs, as such interactions mak
Simplified catechin-gallate inhibitors of HIV-1 reverse transcriptase.
Abstract: Systematic simplification of the molecular structures of epicatechin gallate and epigallocatechin gallate to determine the minimum structural characteristics necessary for HIV-1 reverse transcriptase inhibition in vitro resulted in several compounds that strongly inhibited the native as well as the A17 double mutant (K103N Y181C) enzyme, which is normally insensitive to most known nonnucleoside inhibitors.
Resistance profile and cross-resistance of HIV-1 among patients failing a non-nucleoside reverse transcriptase inhibitor-containing regimen.
Abstract: Among patients failing the nevirapine regimen and presenting with NNRTI mutations, 35 (80%) harboured mutations conferring cross-resistance to efavirenz (K101E, K103N, Y188L) and 9 (20%) harboured mutations conferring resistance to nevirapine alone (V106A and Y181C).
Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012).
Abstract: The most common NVP(R) mutation detected in infants was Y181C.
The biological effects of structural variation at the meta position of the aromatic rings and at the end of the alkenyl chain in the alkenyldiarylmethane series of non-nucleoside reverse transcriptase inhibitors.
PMID: 11708913
2001
Journal of medicinal chemistry
Abstract: Additionally, ADAMs 19 (44-fold) and 21 (29-fold) were more effective against the A98G mutation (found in association with nevirapine resistance in vitro), and ADAM 21 was 5-fold and 2-fold more potent against the Y181C inactivation mutation than the previously reported ADAMs 15 and 17, respectively.
Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients.
Result: As expected, the presence of mutations associated with resistance to non nucleoside reverse transcriptase inhibitors (NNRTIs), only revealed by sequencing analysis showed VI 081 (associated with a reduced drug sensitivity to efavirenz plus nevirapine), V118I (associated with moderate phenotypic lamivudine resistance) and the presence of K103N (key mutation for all the NNRIs) plus Y181C (with variable effects on susceptibility to efavirenz, besides resistance to nevirapine).
Stereochemistry as a major determinant of the anti-HIV activity of chiral naphthyl thiourea compounds.
Abstract: All five 'R' stereoisomers were active anti-HIV agents and inhibited the replication of the HIV-1 strains HTLV-IIIB (NNI-sensitive), A17 (NNI-resistant, Y181C mutant RT) and A17Var (NNI-resistant, Y181C plus K103N mutant RT), as well as primary HIV-1 isolates from AIDS patients in human PBMC at nanomolar concentrations, whereas their enantiomers were inactive.
Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260).
PMID: 10681363
2000
Antimicrobial agents and chemotherapy
Abstract: K103N and Y181C, which confer nonnucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance, were the predominant reverse transcriptase mutations.
Non-nucleoside reverse transcriptase inhibitor resistance among patients failing a nevirapine plus protease inhibitor-containing regimen.
Abstract: Although there is a high degree of cross-resistance among NNRTI, nearly one third of resistant isolates carrying the single Y181C mutation remain susceptible to efavirenz.
Abstract: For isolates containing the single amino acid substitution Y181C, 29% remained fully susceptible to efavirenz, whereas 14% showed intermediate resistance to efavirenz and delavirdine.
Abstract: In the genotypic analysis, the Y181 C mutation was observed in 76% of mutants, and the most common changes were a combination of mutations at positions Y181C/K103N (23%) and the single mutation Y181C (15%).
Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors.
PMID: 10777142
2000
AIDS research and human retroviruses
Abstract: Abacavir plus GW420867X selected only for NNRTI-specific mutations (i.e., K101E, K103R, V106A, and Y181C), including the novel L100V mutation.
HIV mutation literature information.
PMID: 
2001
Journal of molecular biology
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