ArticleAntimicrobial agents and chemotherapy2006
Novel nonnucleoside inhibitors that select nucleoside inhibitor resistance mutations in human immunodeficiency virus type 1 reverse transcriptase.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
- Halo Library, a Tool for Rapid Identification of Ligand Binding Sites on Proteins Using Crystallographic Fragment Screening.Journal of medicinal chemistry · 2023Article
- Structural Basis of HIV-1 Inhibition by Nucleotide-Competing Reverse Transcriptase Inhibitor INDOPY-1.Journal of medicinal chemistry · 2019Article
- Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs.Journal of virology · 2019Article
- Physiological MgBiochemistry · 2017Article
- Pronounced Inhibition Shift from HIV Reverse Transcriptase to Herpetic DNA Polymerases by Increasing the Flexibility of α-Carboxy Nucleoside Phosphonates.Journal of medicinal chemistry · 2015Article
- Derivatives of mesoxalic acid block translocation of HIV-1 reverse transcriptase.The Journal of biological chemistry · 2015Article
- Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor.Antimicrobial agents and chemotherapy · 2015Article
- Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2014Article
- Formation of a quaternary complex of HIV-1 reverse transcriptase with a nucleotide-competing inhibitor and its ATP enhancer.The Journal of biological chemistry · 2013Article
- Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series.Antimicrobial agents and chemotherapy · 2013Article
- HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions.Molecular biology international · 2012Article
- Impact of primer-induced conformational dynamics of HIV-1 reverse transcriptase on polymerase translocation and inhibition.The Journal of biological chemistry · 2011Article
- Identification of low-molecular weight inhibitors of HIV-1 reverse transcriptase using a cell-based high-throughput screening system.Antiviral research · 2011Article
- Subtype-associated differences in HIV-1 reverse transcription affect the viral replication.Retrovirology · 2010Article
- The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity.Antimicrobial agents and chemotherapy · 2010Article
- Reverse transcriptase in motion: conformational dynamics of enzyme-substrate interactions.Biochimica et biophysica acta · 2010Review
- HIV-1 RT Inhibitors with a Novel Mechanism of Action: NNRTIs that Compete with the Nucleotide Substrate.Viruses · 2010Article
- Human immunodeficiency virus type 1 recombinant reverse transcriptase enzymes containing the G190A and Y181C resistance mutations remain sensitive to etravirine.Antimicrobial agents and chemotherapy · 2009Article
- Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors".The Journal of biological chemistry · 2008Article
- A novel nonnucleoside analogue that inhibits human immunodeficiency virus type 1 isolates resistant to current nonnucleoside reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2007Article
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7 authors.
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Abstract
Mutations in and around the catalytic site of the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) are associated with resistance to nucleoside RT inhibitors (NRTIs), whereas changes in the hydrophobic pocket of the RT are attributed to nonnucleoside RT inhibitor (NNRTI) resistance. In this study, we report a novel series of nonnucleoside inhibitors of HIV-1, exemplified by VRX-329747 and VRX-413638, which inhibit both NNRTI- and NRTI-resistant HIV-1 isolates. Enzymatic studies indicated that these compounds are HIV-1 RT inhibitors. Surprisingly, however, following prolonged (6 months) tissue culture selection, this series of nonnucleoside inhibitors did not select NNRTI-resistant mutations in HIV-1 RT. Rather, four mutations (M41L, A62T/V, V118I, and M184V) known to cause resistance to NRTIs and two additional novel mutations (S68N and G112S) adjacent to the catalytic site of the enzyme were selected. Although the M184V mutation appears to be the initial mutation to establish resistance, this mutation alone confers only a two- to fourfold decrease in susceptibility to VRX-329747 and VRX-413638. At least two additional mutations must accumulate for significant resistance. Moreover, while VRX-329747-selected viruses are resistant to lamivudine and emtricitabine due to the M184V mutation, they remain susceptible to zidovudine, stavudine, dideoxyinosine, abacavir, tenofovir, and efavirenz. These results directly demonstrate that VRX-329747 and VRX-413638 are novel nonnucleoside inhibitors of HIV-1 RT with the potential to augment current therapies.
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