# Advancement of poxvirus inhibitor

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $745,122

## Abstract

Abstract
Poxviruses are a large group of human pathogens that include the causative agent of smallpox, Monkeypox, and
Cowpox. As poxvirus immunity around the world wanes there has been a concomitant increase in poxviral
disease, leading to a growing need for small molecule therapeutics that protect against poxviral disease. There
are several investigational drugs that have been used to treat cases of orthopoxvirus infection and one has been
recently approved by the FDA for limited use, but viral resistance to this compound has been noted. The WHO,
CDC and other agencies have stated a strong desire for at least two small molecule therapeutics that broadly
target poxviruses due to the high perceived risk of poxviral disease both from endemic exposure as well as the
potential purposeful release of smallpox as a bioterror agent. This goal has not yet been met.
We have identified a family of non-nucleoside small molecules (“PDPMs”) that show broad spectrum antipoxviral
activity and low/no toxicity to cells and suppress viral mRNA production. Our current data suggests is that the
drug is targeting the poxvirus RNA polymerase (RNAP), which would be an ideal target that is highly conserved
across all poxviruses.
Through this proposal we will probe the potential of PDPMs to become effective antivirals, using medicinal
chemistry approaches to identify compounds with high potency and favorable pharmacokinetic profiles. To aid
and complement the therapeutic development of these molecules, we will use genetic, biochemical and chemical
approaches to determine the target of the compound and the mechanism by which it blocks viral replication.
Following the identification of high potency, pharmacologically favorable compounds, we will test their efficacy
in animal models of poxvirus disease. These experiments will be carried out through an ongoing collaboration at
the CDC. The CDC will oversee testing of PDPMs against smallpox and in efficacy determination in animal
models of poxviral disease.
When these efforts are completed they will enable advanced (towards first-in-human) testing of a new class of
poxvirus inhibitor – an inhibitor that has a mechanism of action complementary to the existing FDA approved
compound and a broad protection profile, fulfilling the need for multi-compound protection from these significant
human pathogens.

## Key facts

- **NIH application ID:** 10808174
- **Project number:** 5R01AI151559-05
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** John H Connor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $745,122
- **Award type:** 5
- **Project period:** 2020-03-12 → 2025-09-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808174

## Citation

> US National Institutes of Health, RePORTER application 10808174, Advancement of poxvirus inhibitor (5R01AI151559-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10808174. Licensed CC0.

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