ArticleScientific reports2018
Inhibition of the precursor and mature forms of HIV-1 protease as a tool for drug evaluation.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Mutational scan of self-cleavage by HIV-1 protease provides new views of a conformationally dynamic mechanism.Journal of virology · 2026Article
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- High-throughput screening and characterization of novel inhibitors targeting HIV-1 protease precursor autoprocessing.Scientific reports · 2025Article
- Mutational scan of self-cleavage by HIV-1 protease provides new views of a conformationally dynamic mechanism.bioRxiv : the preprint server for biology · 2025Article
- The zymogenic form of SARS-CoV-2 main protease: A discrete target for drug discovery.The Journal of biological chemistry · 2025Article
- Mechanism and Kinetics of HIV-1 Protease Activation.Viruses · 2024Review
- Viral proteases as therapeutic targets.Molecular aspects of medicine · 2022Review
- Precursors of Viral Proteases as Distinct Drug Targets.Viruses · 2021Review
- Predicted antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir can potentially bind to neutralize SARS-CoV-2 conserved proteins.Journal of biological research (Thessalonike, Greece) · 2021Article
- Triterpenoid-PEG Ribbons Targeting Selectivity in Pharmacological Effects.Biomedicines · 2021Article
- Darunavir-Resistant HIV-1 Protease Constructs Uphold a Conformational Selection Hypothesis for Drug Resistance.Viruses · 2020Article
- Enrichment of rare events using a multi-parameter high throughput microfluidic droplet sorter.Lab on a chip · 2020Article
- FRET as a biomolecular research tool - understanding its potential while avoiding pitfalls.Nature methods · 2019Review
- Targeting HIV-1 Protease Autoprocessing for High-throughput Drug Discovery and Drug Resistance Assessment.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV-1 protease (PR) is a homodimeric enzyme that is autocatalytically cleaved from the Gag-Pol precursor. Known PR inhibitors bind the mature enzyme several orders of magnitude more strongly than the PR precursor. Inhibition of PR at the precursor level, however, may stop the process at its rate-limiting step before the proteolytic cascade is initiated. Due to its structural heterogeneity, limited solubility and autoprocessing, the PR precursor is difficult to access by classical methods, and limited knowledge regarding precursor inhibition is available. Here, we describe a cell-based assay addressing precursor inhibition. We used a reporter molecule containing the transframe (TFP) and p6* peptides, PR, and N-terminal fragment of reverse transcriptase flanked by the fluorescent proteins mCherry and EGFP on its N- and C- termini, respectively. The level of FRET between EGFP and mCherry indicates the amount of unprocessed reporter, allowing specific monitoring of precursor inhibition. The inhibition can be quantified by flow cytometry. Additionally, two microscopy techniques confirmed that the reporter remains unprocessed within individual cells upon inhibition. We tested darunavir, atazanavir and nelfinavir and their combinations against wild-type PR. Shedding light on an inhibitor's ability to act on non-mature forms of PR may aid novel strategies for next-generation drug design.
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