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Updated: Mar 10, 2026
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High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
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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
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.
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.
