# Evaluation of Optimized Lead Candidates for Encephalitic Alphaviruses in Animal Models

> **NIH NIH U19** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $1,747,217

## Abstract

Program Abstract- Project 2
Currently, there are no licensed human vaccines or antivirals for treating or preventing any encephalitic
alphavirus infection. Because epidemics of alphaviruses are sporadic and unpredictable, and endemic disease
is common (estimated 10,000 cases annually in the Americas) but rarely diagnosed, it is difficult to identify all
populations requiring vaccination; thus, an effective post-exposure treatment method is needed to interrupt
ongoing outbreaks. To address this public health need, we propose a first of its kind small molecule with
prophylactic and therapeutic potential that could be relevant for use both in natural epidemics of V/E/WEEV as
well as a deliberate release scenario. In summary, a successful effort will result in a new class of antiviral drugs
for treatment of encephalitic alphaviruses; Venezuelan (VEEV), Eastern (EEEV) and Western equine
encephalitis viruses (WEEV). Research Project 2 within the U19 Center of Excellence for Encephalitic Alphavirus
Therapeutics program will lead, support and manage testing of optimized lead molecules in animal models for
safety, toxicity, pharmacokinetics and efficacy. The proposed multidisciplinary efforts are focused on
accomplishing studies (Aims 1 and 2) that together with Research Project 1 and 3 will inform selection of the
best leads for Technology Readiness Level 5 studies (medicalcountermeasures.gov) mid-way through the
program (i.e. Aims 3 and 4). Aim 1 will assess lead optimized molecules for broad spectrum efficacy, PK and
dose range finding studies in mouse models and preliminary safety in rat in years 1-3. Aim 2 will assess four
lead optimized molecules for therapeutic window, dosing, delay of treatment to define dosing regimen and
potential indications for treatment in lethal mouse models of V/E/WEEV in years 1-3. Aim 3 will evaluate lead
candidate molecules with favorable criteria in nonGLP and GLP rat and non-human primate (NHP) safety, PK
and toxicokinetic studies in collaboration with BASi, a commercial research organization. The pivotal efficacy
studies in Aim 4 will evaluate the efficacy of the best lead quinazolinone in two animal species, mouse and
cynomolgus monkeys, using dosing regimens defined in the preceding 3-4 years. The Center has two planned
meetings with the FDA, one informal meeting mid-way through the program and one formal meeting prior to the
efficacy studies in NHP in Aim 4. These studies will contribute to the reports to be readied by our consultants at
Leidos.

## Key facts

- **NIH application ID:** 9886198
- **Project number:** 5U19AI142762-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Colleen B Jonsson
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,747,217
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886198

## Citation

> US National Institutes of Health, RePORTER application 9886198, Evaluation of Optimized Lead Candidates for Encephalitic Alphaviruses in Animal Models (5U19AI142762-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9886198. Licensed CC0.

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