# Broad-spectrum inhibitors targeting the viral replication promoter conserved in dengue and Zika viruses

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $193,464

## Abstract

Project Summary
Zika virus (ZIKV) and dengue virus (DENV) are mosquito-borne flaviviruses that cause disease ranging in
severity from mild symptoms to deadly hemorrhagic dengue fever. ZIKV was rapidly spreading five years ago
to over 20 countries in South and Central America, where infections by ZIKV reached pandemic levels and
threatened to expand to the southern US. The threat by DENV has increased dramatically over the last two
decades as one of the worst mosquito-borne pathogens in tropical regions. To treat outbreaks of DENV in
ZIKV-endemic regions, and vice versa, broad-spectrum inhibitor drugs against mosquito-borne flaviviruses
would provide an efficient therapeutic approach that reduces the risk of immuno-associated exacerbation, for
example in previously infected or vaccinated patients.
Sequence alignment of DENV and ZIKV clinical isolates in combination with secondary structure prediction
have led us to identify a conserved RNA three-way junction that serves as the replication promoter in
flaviviruses. Here, we propose to identify compounds that inhibit viral replication by targeting the promoter RNA
as lead candidates for the future development of DENV and ZIKV broad-spectrum therapeutics.
The Specific Aims of this proposal are to 1) develop a FRET-based binding assay to assess small molecules
as selective ligands of the DENV and ZIKV replication promoter RNA, 2) establish an in vitro replication
initiation assay to identify promoter RNA-binding ligands as inhibitors of ZIKV replication, and 3) discover small
molecules that inhibit DENV and ZIKV in cell culture by targeting the RNA 3WJ motif that serves as the viral
replication promoter.

## Key facts

- **NIH application ID:** 10381583
- **Project number:** 5R21AI159643-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Thomas C Hermann
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,464
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381583

## Citation

> US National Institutes of Health, RePORTER application 10381583, Broad-spectrum inhibitors targeting the viral replication promoter conserved in dengue and Zika viruses (5R21AI159643-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10381583. Licensed CC0.

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