ArticlePLoS pathogens2006
Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.
Article in PLoS pathogens, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks.BMC systems biology · 2010Pooled it
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- Conformational Dynamics of Viral Protease Precursors in Maturation, Inhibition, and Drug-Resistance Development.Viruses · 2026Review
- Real-Time Imaging of HIV-1 Protease Activation and Substrate Cleavage in Single Virions Assembling on the Plasma Membrane.Viruses · 2026Article
- Cotranslational Folding and "Constrained Monomers" in the Maturation of HIV-1 Protease.Journal of molecular biology · 2026Article
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- Evasion of CARD8 activation during HIV-1 assembly.Science advances · 2025Article
- A virus-like particle assembly system for probing the HIV-1 Gag-Pol dimerization domain: supporting evidence for reverse transcriptase involvement in protease activation by influencing Gag-Pol/Gag-Pol interaction.Journal of virology · 2025Article
- Mechanistic basis for a novel dual-function Gag-Pol dimerizer potentiating CARD8 inflammasome activation and clearance of HIV-infected cells.npj drug discovery · 2025Article
- Mechanism and Kinetics of HIV-1 Protease Activation.Viruses · 2024Review
- CROI 2024: Summary of Basic Science Research in HIV.Topics in antiviral medicine · 2024Article
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- HIV-1 reverse transcriptase stability correlates with Gag cleavage efficiency: reverse transcriptase interaction implications for modulating protease activation.Journal of virology · 2023Article
- Article
- Chemical inhibition of DPP9 sensitizes the CARD8 inflammasome in HIV-1-infected cells.Nature chemical biology · 2023Article
- CARD8 Inflammasome Activation by HIV-1 Protease.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Role of pyroptosis in inflammation and cancer.Cellular & molecular immunology · 2022Review
- Beyond Inhibition: A Novel Strategy of Targeting HIV-1 Protease to Eliminate Viral Reservoirs.Viruses · 2022Review
- Effects of reduced gag cleavage efficiency on HIV-1 Gag-Pol package.BMC microbiology · 2022Article
- Amino acid substitutions at the HIV-1 transframe region significantly impair virus infectivity.PloS one · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) target HIV-1 reverse transcriptase (RT) by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.