ArticlePLoS pathogens2011
Inhibition of both HIV-1 reverse transcription and gene expression by a cyclic peptide that binds the Tat-transactivating response element (TAR) RNA.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
38 citing papers in PubMed, 78 citations in OpenAlex.
- The kinase inhibitor palbociclib binds to HIV TAR RNA with very low nanomolar affinity and exquisite specificity.Nucleic acids research · 2026Article
- Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2.International journal of molecular sciences · 2024Article
- A Novel Time-Resolved Fluorescence Resonance Energy Transfer Assay for the Discovery of Small-Molecule Inhibitors of HIV-1 Tat-Regulated Transcription.International journal of molecular sciences · 2023Article
- A Tripartite Complex HIV-1 Tat-Cyclophilin A-Capsid Protein Enables Tat Encapsidation That Is Required for HIV-1 Infectivity.Journal of virology · 2023Article
- Drug-Like Small Molecules That Inhibit Expression of the Oncogenic MicroRNA-21.ACS chemical biology · 2023Article
- Enhancement of CD4 Binding, Host Cell Entry, and Sensitivity to CD4bs Antibody Inhibition Conferred by a Natural but Rare Polymorphism in the HIV-1 Envelope.Journal of virology · 2022Article
- RNA-Binding Macrocyclic Peptides.Frontiers in molecular biosciences · 2022Review
- Addressing an HIV cure in LMIC.Retrovirology · 2021Review
- Recent Trends in Cyclic Peptides as Therapeutic Agents and Biochemical Tools.Biomolecules & therapeutics · 2020Review
- Face-time with TAR: Portraits of an HIV-1 RNA with diverse modes of effector recognition relevant for drug discovery.The Journal of biological chemistry · 2019Review
- Understanding the Contributions of Conformational Changes, Thermodynamics, and Kinetics of RNA-Small Molecule Interactions.ACS chemical biology · 2019Review
- A Small Cyclic β-Hairpin Peptide Mimics the Rbfox2 RNA Recognition Motif and Binds to the Precursor miRNA 20b.Chembiochem : a European journal of chemical biology · 2019Article
- An ultra-high affinity ligand of HIV-1 TAR reveals the RNA structure recognized by P-TEFb.Nucleic acids research · 2019Article
- Molecular recognition of HIV-1 RNAs with branched peptides.Methods in enzymology · 2019Article
- The role of exosomal transport of viral agents in persistent HIV pathogenesis.Retrovirology · 2018Review
- Potent Inhibition of Hepatitis E Virus Release by a Cyclic Peptide Inhibitor of the Interaction between Viral Open Reading Frame 3 Protein and Host Tumor Susceptibility Gene 101.Journal of virology · 2018Article
- Structure of HIV TAR in complex with a Lab-Evolved RRM provides insight into duplex RNA recognition and synthesis of a constrained peptide that impairs transcription.Nucleic acids research · 2018Article
- Review of Current Cell-Penetrating Antibody Developments for HIV-1 Therapy.Molecules (Basel, Switzerland) · 2018Review
- A Macrocyclic Peptide Ligand Binds the Oncogenic MicroRNA-21 Precursor and Suppresses Dicer Processing.ACS chemical biology · 2017Article
- Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction.Frontiers in microbiology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
The RNA response element TAR plays a critical role in HIV replication by providing a binding site for the recruitment of the viral transactivator protein Tat. Using a structure-guided approach, we have developed a series of conformationally-constrained cyclic peptides that act as structural mimics of the Tat RNA binding region and block Tat-TAR interactions at nanomolar concentrations in vitro. Here we show that these compounds block Tat-dependent transcription in cell-free systems and in cell-based reporter assays. The compounds are also cell permeable, have low toxicity, and inhibit replication of diverse HIV-1 strains, including both CXCR4-tropic and CCR5-tropic primary HIV-1 isolates of the divergent subtypes A, B, C, D and CRF01_AE. In human peripheral blood mononuclear cells, the cyclic peptidomimetic L50 exhibited an IC(50) ∼250 nM. Surprisingly, inhibition of LTR-driven HIV-1 transcription could not account for the full antiviral activity. Timed drug-addition experiments revealed that L-50 has a bi-phasic inhibition curve with the first phase occurring after HIV-1 entry into the host cell and during the initiation of HIV-1 reverse transcription. The second phase coincides with inhibition of HIV-1 transcription. Reconstituted reverse transcription assays confirm that HIV-1 (-) strand strong stop DNA synthesis is blocked by L50-TAR RNA interactions in-vitro. These findings are consistent with genetic evidence that TAR plays critical roles both during reverse transcription and during HIV gene expression. Our results suggest that antiviral drugs targeting TAR RNA might be highly effective due to a dual inhibitory mechanism.
Indexed as
Identifiers
What OpenQuestion holds
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.