Evidence map›Paper›PMID 31080171›Full record

ReviewThe Journal of biological chemistry2019

Face-time with TAR: Portraits of an HIV-1 RNA with diverse modes of effector recognition relevant for drug discovery.

Sai Shashank Chavali, Rachel Bonn-Breach, Joseph E Wedekind

Open access · hybridAbstract readReview
In one paragraph

Review in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. HIV-1 Transcription Inhibition Using Small RNA-Binding Molecules.Pharmaceuticals (Basel, Switzerland) · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Sai Shashank ChavaliFrom the Department of Biochemistry and Biophysics, Center for RNA Biology, and Center for AIDS Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
Rachel Bonn-BreachFrom the Department of Biochemistry and Biophysics, Center for RNA Biology, and Center for AIDS Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
Joseph E WedekindFrom the Department of Biochemistry and Biophysics, Center for RNA Biology, and Center for AIDS Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 joseph.wedekind@rochester.edu.ORCID 0000-0002-4269-4229
University of Rochester · US

Funding

Virology/Immunology CoreP30AI078498 · NIAID · UNIVERSITY OF ROCHESTER · PI DEWHURST, STEPHEN · 2008 to 2018
$14.6M
Mechanisms of Action On Non-Coding RNA MoleculesR01GM063162 · NIGMS · UNIVERSITY OF ROCHESTER · PI WEDEKIND, JOSEPH E · 2001 to 2024
$6.8M
Cyclic Peptide Inhibitors of HIV-1 ProliferationR01GM123864 · NIGMS · UNIVERSITY OF ROCHESTER · PI KENNAN, ALAN J, WEDEKIND, JOSEPH E · 2017 to 2018
$797k
Cyclic Peptide Inhibitors of HIV-1 ProliferationR01AI150463 · NIAID · UNIVERSITY OF ROCHESTER · PI WEDEKIND, JOSEPH E · 2019 to 2020
$774k
NIAID NIH HHS P30 AI078498NIAID NIH HHS R01 AI150463NIGMS NIH HHS R01 GM063162NIGMS NIH HHS R01 GM123864
6 · The paper itself

Abstract

Small molecules and short peptides that potently and selectively bind RNA are rare, making the molecular structures of these complexes highly exceptional. Accordingly, several recent investigations have provided unprecedented structural insights into how peptides and proteins recognize the HIV-1 transactivation response (TAR) element, a 59-nucleotide-long, noncoding RNA segment in the 5' long terminal repeat region of viral transcripts. Here, we offer an integrated perspective on these advances by describing earlier progress on TAR binding to small molecules, and by drawing parallels to recent successes in the identification of compounds that target the hepatitis C virus internal ribosome entry site (IRES) and the flavin-mononucleotide riboswitch. We relate this work to recent progress that pinpoints specific determinants of TAR recognition by: (i) viral Tat proteins, (ii) an innovative lab-evolved TAR-binding protein, and (iii) an ultrahigh-affinity cyclic peptide. New structural details are used to model the TAR-Tat-super-elongation complex (SEC) that is essential for efficient viral transcription and represents a focal point for antiviral drug design. A key prediction is that the Tat transactivation domain makes modest contacts with the TAR apical loop, whereas its arginine-rich motif spans the entire length of the TAR major groove. This expansive interface has significant implications for drug discovery and design, and it further suggests that future lab-evolved proteins could be deployed to discover steric restriction points that block Tat-mediated recruitment of the host SEC to HIV-1 TAR.

Indexed as

Drug DiscoveryAntiviral AgentsHIV-1HIV InfectionsHIV Long Terminal RepeatHumansRNA, Viraltat Gene Products, Human Immunodeficiency VirusTranscription, GeneticAntiviral AgentsRNA, Viraltat Gene Products, Human Immunodeficiency Virusarginine-sandwich motifdrug developmentdrug discoveryHIV TAR RNARNA-binding proteinRNA–drug interactionRNA–protein interactionRNA structureRNA virusstructural biologystructural modelstructure–functionsuper-elongation complexviral transactivation

Identifiers

PMID31080171
PMCPMC6579462
OpenAlexW2944987824

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.