# Combating Corneal HSV Infection with Novel Dynasore Analogues

> **NIH NIH R41** · MEDCHEM PARTNERS, LLC · 2024 · $180,642

## Abstract

PROJECT SUMMARY
Herpes simplex viruses 1 and 2 (HSV-1, -2) are epidemic worldwide. Globally, it has been estimated that
approximately 1.5 million cases of HSV-related ocular infection occur every year, with 40,000 of those ending
up with longstanding visual damage. The virus’s ability to spread through airborne droplets contributes to its
high degree of transmissibility, often leading to blinding corneal ulcers. Current standards of care include
concurrent treatment with anti-virals and corticosteroids, which are effective, but have side effects that can
compromise visual acuity. Similarly, during severe inflammatory conditions, corneal transplantation is required
to preserve vision. Therefore, there is a need to develop therapies that can prevent or reduce the ability of
HSV-1 to infect ocular surface epithelial cells, which would then mitigate subsequent inflammation and loss of
visual acuity. It has been suggested that molecules contributing to more than one step in the HSV life cycle
may serve more effectively as targets for new preventative or therapeutic drugs. Dynasore is a cell-permeant
small molecule developed to target the GTPase activities of classic dynamins, a family of molecules that
participate in several endocytic pathways and in several steps in the HSV life cycle. Indeed, dynasore has
been demonstrated to have pleiotropic effects against HSV infection, including inhibition of cell uptake,
intracellular trafficking, capsid assembly, and cell-to-cell spread. The applicant company recently undertook a
project to develop dynasore analogues to protect against epitheliopathy in dry eye (DE) disease. The team
identified 3 lead compounds that inhibit clathrin-mediated endocytosis with greater potency than dynasore.
Two of the leads are novel chemical entities (NCEs) substantially different from dynasore, thus are likely to be
patentable. Importantly, the team now demonstrates their antiviral effect specifically against HSV infection of
corneal mucosal epithelial cells in culture, although with different rank potencies than for cytoprotection. The
goal of this proposal is to refine the structure-activity relationship for antiviral effect against HSV. From this
screen, up to 5 lead compounds with optimized anti-HSV1 profiles will be selected. Then, using a mouse
model of HSK, the most efficacious compound(s) will be identified to take forward for further development.
Following completion of this Phase I effort, the team will have defined the SAR for inhibition of HSV-1 infection
and HSK in a mouse model. During Phase II, the team will prepare additional compounds to evaluate
absorption, distribution, metabolism and excretion (ADME) properties as well as physicochemical and
pharmacokinetic (PK) measurements. Finally, the team will fine tune the formulation and dosage to maximize
efficacy, shelf life and ease of application, while decreasing any toxic or off-target effects.

## Key facts

- **NIH application ID:** 10820367
- **Project number:** 1R41EY035879-01
- **Recipient organization:** MEDCHEM PARTNERS, LLC
- **Principal Investigator:** Tsvetelina Ivanonova Lazarova
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $180,642
- **Award type:** 1
- **Project period:** 2024-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820367

## Citation

> US National Institutes of Health, RePORTER application 10820367, Combating Corneal HSV Infection with Novel Dynasore Analogues (1R41EY035879-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10820367. Licensed CC0.

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