ArticleACS chemical biology2009
Selection and characterization of small molecules that bind the HIV-1 frameshift site RNA.
Article in ACS chemical biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Programmable modulation of ribosomal frameshifting by mRNA targeting CRISPR-Cas12a system.iScience · 2023Article
- Structural and Functional Insights into Viral Programmed Ribosomal Frameshifting.Annual review of virology · 2023Review
- Thinking Outside the Frame: Impacting Genomes Capacity by Programmed Ribosomal Frameshifting.Frontiers in molecular biosciences · 2022Review
- A Novel Frameshifting Inhibitor Having Antiviral Activity against Zoonotic Coronaviruses.Viruses · 2021Article
- An RNA pseudoknot stimulates HTLV-1RNA (New York, N.Y.) · 2020Article
- Approved Anti-cancer Drugs Target Oncogenic Non-coding RNAs.Cell chemical biology · 2018Article
- Translation Elongation and Recoding in Eukaryotes.Cold Spring Harbor perspectives in biology · 2018Review
- Stability of HIV Frameshift Site RNA Correlates with Frameshift Efficiency and Decreased Virus Infectivity.Journal of virology · 2016Article
- A general strategy to inhibiting viral -1 frameshifting based on upstream attenuation duplex formation.Nucleic acids research · 2016Article
- Dynamic motions of the HIV-1 frameshift site RNA.Biophysical journal · 2015Article
- Highly conserved RNA pseudoknots at the Gag-Pol junction of HIV-1 suggest a novel mechanism of -1 ribosomal frameshifting.RNA (New York, N.Y.) · 2014Article
- High-affinity recognition of HIV-1 frameshift-stimulating RNA alters frameshifting in vitro and interferes with HIV-1 infectivity.Journal of medicinal chemistry · 2014Article
- Influence of dimethylsulfoxide on RNA structure and ligand binding.Analytical chemistry · 2013Article
- HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome.Nucleic acids research · 2013Article
- Modulation of ribosomal frameshifting frequency and its effect on the replication of Rous sarcoma virus.Journal of virology · 2012Article
- Chemical correction of pre-mRNA splicing defects associated with sequestration of muscleblind-like 1 protein by expanded r(CAG)-containing transcripts.ACS chemical biology · 2012Article
- Targeting frameshifting in the human immunodeficiency virus.Expert opinion on therapeutic targets · 2012Review
- Anti-Japanese-encephalitis-viral effects of kaempferol and daidzin and their RNA-binding characteristics.PloS one · 2012Article
- Structure of the HIV-1 frameshift site RNA bound to a small molecule inhibitor of viral replication.ACS chemical biology · 2011Article
- Anti-viral opportunities during transcriptional activation of latent HIV in the host chromatin.Methods (San Diego, Calif.) · 2011Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
HIV-1 requires a -1 translational frameshift to properly synthesize the viral enzymes required for replication. The frameshift mechanism is dependent upon two RNA elements, a seven-nucleotide slippery sequence (UUUUUUA) and a downstream RNA structure. Frameshifting occurs with a frequency of approximately 5%, and increasing or decreasing this frequency may result in a decrease in viral replication. Here, we report the results of a high-throughput screen designed to find small molecules that bind to the HIV-1 frameshift site RNA. Out of 34,500 compounds screened, 202 were identified as positive hits. We show that one of these compounds, doxorubicin, binds the HIV-1 RNA with low micromolar affinity (K(d) = 2.8 microM). This binding was confirmed and localized to the RNA using NMR. Further analysis revealed that this compound increased the RNA stability by approximately 5 degrees C and decreased translational frameshifting by 28% (+/-14%), as measured in vitro.
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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.