# Discovery of antiviral inhibitors for the treatment of orthopoxvirus infections

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

## Abstract

PROJECT SUMMARY
Smallpox (caused by variola virus infection) was one of the most destructive diseases in human history,
resulting in 300-500 million deaths in the twentieth century alone until it was finally eradicated in 1980.
Following elimination of variola virus, global vaccination programs were eventually halted and as a result, most
of the world’s population is no longer immunologically protected from smallpox nor does it enjoy cross-
protection to other orthopoxviruses. There are two drugs approved for smallpox disease, however, both
compounds possess significant limitations. A lack of therapeutic options for treating orthopoxvirus infections
continues to expose the population to grave risk from a smallpox bioweapon as well as future zoonotic
orthopoxvirus infections. During the course of the Phase I funding period, we will execute a hit finding
campaign against a library of >200,000 compounds with optimal drug-like properties. Quality hits that emerge
from the assay will be subjected to follow-on testing that will investigate the potency, selectivity, and
mechanism of action. The most interesting of these compounds will be subjected to medicinal chemistry driven
hit-to-lead to explore structure-activity relationships (SAR). The overall goal of this project is to discover one or
more novel lead series which is defined as a chemotype inhibitor that demonstrates tractable SAR, potent
antiviral activity against variola virus and other orthopoxviruses with minimal cytotoxicity. Success in these
endeavors will trigger the submission of a Phase II application that will advance the program from Early Lead
Optimization through to Candidate Selection.

## Key facts

- **NIH application ID:** 10892864
- **Project number:** 5R43AI179443-02
- **Recipient organization:** VENATORX PHARMACEUTICALS, INC.
- **Principal Investigator:** Glen Coburn
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2023-07-24 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892864

## Citation

> US National Institutes of Health, RePORTER application 10892864, Discovery of antiviral inhibitors for the treatment of orthopoxvirus infections (5R43AI179443-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892864. Licensed CC0.

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