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Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
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Targeting dengue virus infection through a translation-modulator small-molecule screen.

Rodolfo Katz1, Yarden Moalem1, Rina Rosin-Arbesfeld1

  • 1Department of Clinical Microbiology and Immunology, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.

Antiviral Research
|March 9, 2026
PubMed
Summary

Researchers screened translation modulators to find new dengue virus (DENV) treatments. Elongation inhibitors showed strong antiviral effects, offering potential for new therapies against this mosquito-borne virus.

Keywords:
Dengue virusHost-targeted antiviralsTranslation elongationTranslation modulatorsZika virus

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Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Dengue virus (DENV) is a significant global health threat due to limited treatment options.
  • Developing host-targeted antivirals is crucial for combating DENV.
  • Understanding viral replication mechanisms can reveal new therapeutic strategies.

Purpose of the Study:

  • To identify host-targeted vulnerabilities in DENV replication.
  • To screen small-molecule translation modulators for antiviral activity.
  • To evaluate the potential of identified compounds as DENV therapeutics.

Main Methods:

  • Functional screening of small-molecule translation modulators.
  • Assessing antiviral effects by measuring viral RNA, protein levels, and infectious virus production.
  • Testing inhibitors in cell lines and primary human macrophages.

Main Results:

  • Translation elongation inhibitors demonstrated potent antiviral activity against DENV.
  • Compounds targeting eIF4A helicase, like Rocaglamide A, showed strong DENV suppression.
  • Clinically relevant inhibitors homoharringtonine (HHT) and bruceantin (BCT) effectively blocked DENV propagation at low nanomolar concentrations.
  • Similar antiviral effects were observed for Zika virus (ZIKV).

Conclusions:

  • Translation elongation and eIF4A helicase activity represent potential host dependencies for Orthoflaviviruses.
  • HHT and BCT show promise as DENV therapeutics, warranting further in vivo and stage-resolved studies.
  • Targeting host translation machinery offers a viable strategy for developing broad-spectrum flavivirus antivirals.