Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture.
Abstract: In contrast, the Y181C reverse transcriptase demonstrated a selective acceleration of the secondary RNase H cleavage step during both modes of RNase H cleavage.
Abstract: Of the NNRTI-resistant mutants, V179D was more fit than Y181C, and both of these mutants were more fit than V106A, which demonstrated the greatest reduction in RNase H cleavage.
Abstract: Three mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (V106A, V179D, and Y181C), which occur in clinical isolates and confer resistance to nonnucleoside reverse transcriptase inhibitors (
Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase.
Abstract: HI-511 R inhibited the HIV-strain A17 variant, containing RT mutations Y181C plus K103N, with an IC50 value of 2.7 microM, whereas the IC50 values of nevirapine, delavirdine, and trovirdine against this highly NNI-resistant HIV-1 strain were >100 microM.
Abstract: When tested against the NNI-resistant HIV-1 strain A17 with a Y181C mutation in RT, HI-511R was found to be 10,000-times more active than nevirapine, 5000-times more active than delavirdine, and 50-times more active than trovirdine.
Structure-based drug design of non-nucleoside inhibitors for wild-type and drug-resistant HIV reverse transcriptase.
Abstract: Modeling studies revealed that for an NNI of HIV RT to be active against RT mutants such as the especially problematic Y181C RT mutant, the following features are required: (a) the inhibitor should be highly potent against wild-type RT and therefore capable of tolerating a considerable activity loss against RT mutants.
Genetic diversity of protease and reverse transcriptase sequences in non-subtype-B human immunodeficiency virus type 1 strains: evidence of many minor drug resistance mutations in treatment-naive patients.
PMID: 11060045
2000
Journal of clinical microbiology
Abstract: Major mutations linked to resistance to non-NRTI agents were detected in all group O isolates (A98G and Y181C) and in one subtype J virus (V108I).
Piperidinylethyl, phenoxyethyl and fluoroethyl bromopyridyl thiourea compounds with potent anti-HIV activity.
Abstract: Notably, the lead fluorothiourea compounds 11 and 12 were both substantially more active against the NNRTI-resistant HIV strains RT-MDR (V106A) and A17 (Y181C) than nevirapine or delavirdine.
Three-dimensional quantitative structure-activity relationships study on HIV-1 reverse transcriptase inhibitors in the class of dipyridodiazepinone derivatives, using comparative molecular field analysis.
PMID: 11155314
2000
Journal of molecular graphics & modelling
Abstract: A three-dimensional quantitative structure-activity relationships (3D QSAR) method, Comparative Molecular Field Analysis (CoMFA), was applied to a set of dipyridodiazepinone (nevirapine) derivatives active against wild-type (WT) and mutant-type (Y181C) HIV-1 reverse transcriptase.
Abstract: CoMFA contour maps reveal that steric and electrostatic interactions corresponding to the WT inhibition amount to 58.5% and 41.5%, respectively, while steric and electrostatic effects have approximately equal contributions for the explanation of inhibitory activities against Y181C.
Abstract: CoMFA was used to discriminate between structural requirements for WT and Y181C inhibitory activities.
Abstract: The resulting CoMFA models yield satisfactory predictive ability regarding WT and Y181C inhibitions, wit
Calanolides, the naturally occurring anti-HIV agents.
PMID: 19649847
2000
Current opinion in drug discovery & development
Abstract: Further enhancement of activity is observed with RTs that possess the Y181C change together with AZT-resistant mutations.
Abstract: Moreover, when challenged with viruses containing Y181C and K103N dual mutations, calanolide compounds remain active.
Abstract: Of particular interest is the use of calanolide in the treatment of patients who have failed other NNRTI therapy and developed the Y181C mutation or the Y181C/K103N dual mutations.
Abstract: These compounds also exhibit an enhanced antiviral activity against one of the most prevalent non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant vir
Argentine plant extracts active against polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.
Abstract: 4) were examined in vitro for their ability to inhibit the polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (wild and Y181C mutant types).
Abstract: These extracts were refractioned into four fractions; 2I4 and 4I4 were active as inhibitors of DNA-polymerase (wild and Y181C types) and RNase H activities.
Rational design of N-[2-(2,5-dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus.
Abstract: RT assays revealed that HI-236 was not only more potent than trovirdine, MKC-442, and AZT against the drug-sensitive HIV-1 strain HTLV(IIIB), it was also 50-100 times more effective than delavirdine or nevirapine and twice as effective as our recently reported lead compound N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-240) against the NNI-resistant Y181C mutant HIV-1 strain A17.
Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide.
PMID: 10428899
1999
Antimicrobial agents and chemotherapy
Abstract: Further enhancement of activity is observed with RTs that possess the Y181C change together with mutations that yield resistance to AZT.
Abstract: The calanolide analogs, however, exhibit 10-fold enhanced antiviral activity against drug-resistant viruses that bear the most prevalent NNRTI resistance that is engendered by amino acid change Y181C in the RT.
HIV mutation literature information.
PMID: 
2000
Journal of virology
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