# Development of a Small Molecule Inhibitor to Eradicate HSV Latent Infection in Neurons

> **NIH NIH R43** · VIRONIKA, LLC · 2020 · $300,000

## Abstract

Summary
 Chronic, long-term infection with herpes simplex virus (HSV) remains a significant
unmet medical need. It is estimated that ~800,000 individuals in the US will be newly
infected with HSV1 or HSV2 each year, and that the total infection rate approaches 80%
for adults over 50 yrs of age. Long-term latent infection and chronic reactivation of HSV1
and HSV2 remain a significant source of morbidity, including a major source of blindness
and encephalitis. Presently, there are no vaccines or small molecule drugs that
selectively treat and eliminate the latent infection. Here, we propose to develop new
chemical entity small molecule drugs to target and treat latent forms of HSV infection in
human neurons. HSV express only one viral transcript, termed LAT, during neuronal
latency. LAT is known to be a stable intron that is highly conserved among all viral
strains across both HSV1 and HSV2 species. LAT is important for maintaining viral
latency and confers resistance to apoptosis for latently infected neurons. The most
highly conserved substructure of LAT is the stable 3’ stem loop containing a non-
canonical branch point sequence that prevents debranching by the cellular enzyme
DBR1. Genetic studies reveal that disruption of the stem-loop and branch point
structure destabilizes LAT and eliminates its functional activity. Here, we propose to
carry out high-throughput screenings with the recently developed FRET-based
biochemical assay and will develop and implement cell-based assays to identify
selective interacting, RNA-structure disrupting molecules that have favorable drug-like
properties using industry standard principles of medicinal chemistry and fragment-based
drug design.
 The product that ultimately results from this proposal is a small molecule inhibitor
that selectively binds and disrupts the function of LAT RNA in HSV neuronal latency, and
can be further developed for the treatment of HSV latency and associated diseases.

## Key facts

- **NIH application ID:** 9989783
- **Project number:** 5R43AI142976-02
- **Recipient organization:** VIRONIKA, LLC
- **Principal Investigator:** Takahiro Yano
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2019-08-06 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989783

## Citation

> US National Institutes of Health, RePORTER application 9989783, Development of a Small Molecule Inhibitor to Eradicate HSV Latent Infection in Neurons (5R43AI142976-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989783. Licensed CC0.

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