# Targeted RNA degradation assay for new antiviral drug discovery

> **NIH NIH R43** · LUCERNA, INC. · 2024 · $300,000

## Abstract

PROJECT SUMMARY
There are currently no effective vaccines or antiviral drugs for most of the viral diseases afflicting
human. Development of new therapy is challenging and expensive, and often complicated by
drug resistance. It is now known that viral transcripts contain many highly structured RNA
elements in both the coding and noncoding regions, and they play key roles in the viral life cycle.
Many of these elements are highly conserved and, thus, they are attractive new targets that
potentially have lower likelihoods of viral resistance development. Targeted RNA degradation
(TRD) is an emerging strategy in recent efforts to further discover new antiviral small molecules
with privileged scaffolds and better resistance profiles. However, early-stage TRD drug discovery
has been hindered by current high-throughput screening (HTS) assay technologies designed for
protein targets. Virtually all cell-based drug screens used minigene reporters that rely on
luciferase or fluorescent protein signals for assay read-out. Minigene reporter design is
straightforward but minigene reporter requires mRNA export to the cytosol and protein translation.
This significantly increases the rate of false hits per screen since compounds that inhibit global
protein translation machinery or RNA export will also impact reporter read-out. Assays that
monitor endogenous RNA levels are low-throughput or time-consuming, involve multiple steps,
and not readily adaptable for high-throughput SM screening. Thus, there is an unmet need for a
new cell-based HTS assay platform that monitors target RNA turnover directly, reflects real-time
RNA dynamics, and compatible for different types of RNA and different TRD approaches. For
proof-of-concept, this project aims to develop HTS-compatible reporters that can measure drug-
induced changes of RNA levels of dengue and influenza viruses, two global pathogens with
different genomic structures and life cycles. The ultimate product of this SBIR project will be a
cell-based HTS assay platform that can accelerate the early-stage discovery of TRD drugs toward
previously intractable viral diseases.

## Key facts

- **NIH application ID:** 11006184
- **Project number:** 1R43AI186768-01
- **Recipient organization:** LUCERNA, INC.
- **Principal Investigator:** Ryan O'Hanlon
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11006184

## Citation

> US National Institutes of Health, RePORTER application 11006184, Targeted RNA degradation assay for new antiviral drug discovery (1R43AI186768-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11006184. Licensed CC0.

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