# A small molecule inhibitor of HSV genital infections

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $399,750

## Abstract

Abstract
Genital herpes is a sexually transmitted disease primarily caused by herpes simplex virus type 2 (HSV-2). An
estimated 20% of the population in the US is infected with HSV-2. Adding to the problems and diseases
afflicted by HSV-2 infections, cases of genital infections by HSV-1 have gone up significantly in the past few
decades. This creates a complex health issue since much higher percentages of adults may harbor HSV-1. HSV
belongs to a subfamily of neurotropic herpesviruses that establish latency in sensory neurons and cause lifelong
recurrent infections. Current frontline treatments against genital herpes include acyclovir (ACV) and its
analogs. While these have proven effective over the past few decades, the limitations associated with these
antivirals such as: a) increasing incidences of drug resistance especially among immunocompromised patients,
b) limited efficacy as topical formulations, and c) higher cost of treatment and side effects associated with long-
term systemic treatments, restrict their use and underscore the need for new and improved treatment options.
The focus of this study is to evaluate the efficacy of a small molecule, Iazovir (IZV), as a viable alternative
treatment for genital herpes. We have strong and supportive preliminary data to develop IZV as a brand new
class of highly effective antivirals. Two specific aims are proposed that will establish the efficacy and provide
the molecular mechanism behind the antiviral action of IZV. Aim 1 will focus on determining the mechanism of
antiviral action by IZV. Based on our interesting preliminary results that IZV reduces both HSV genome and
transcript levels, we hypothesize that IZV can: (i) block transcription of HSV-2 genomes by TANK binding
kinase 1 (TBK1)-mediated modulation of NF-B activation and (ii) inhibit HSV-2 replication through its
suppressive activity on nuclear mitotic apparatus (NuMA). Multiple experiments are planned to test our
hypothesis. In parallel, IZV resistant HSV-2 mutants will be generated to provide an unbiased and deeper
understanding of the mechanisms that govern the antiviral potential of IZV. Aim 2 will use mouse models of
genital HSV-2 infection to determine the in vivo preclinical efficacy of IZV treatment as a topical and oral
antiviral therapy. Experiments will also be undertaken to demonstrate IZV’s high efficacy as an oral treatment
against murine genital infections caused by HSV-1. We will also determine the acute and chronic toxicities
induced by IZV treatment in order to fully characterize its pre-clinical efficacy. Successful completion of our
studies will establish IZV as a new class of HSV antivirals ready for future clinical trials and studies.

## Key facts

- **NIH application ID:** 9984156
- **Project number:** 5R01AI139768-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** DEEPAK SHUKLA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 2018-08-14 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984156

## Citation

> US National Institutes of Health, RePORTER application 9984156, A small molecule inhibitor of HSV genital infections (5R01AI139768-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9984156. Licensed CC0.

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