# Medicinal Chemistry Optimization of Anti-Alphaviral Leads and Elucidation of Target and Off Target Engagement

> **NIH NIH U19** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2022 · $583,618

## Abstract

Venezuelan (VEEV), Western (WEEV), and Eastern Equine Encephalitis viruses (WEEV), are
emerging pathogens that cause human encephalitis, yet there are no approved human vaccines
or antiviral agents for treating or preventing any alphaviruses infection. Our research objectives
include the development of a broad spectrum antiviral clinical candidate against these
encephalitic alphavirus infections in humans. The aims of Research Project 1 within the U19
Center of Excellence for Encephalitic Alphavirus Therapeutics (CEEAT) program focus on the
lead optimization activities of two distinct small molecule scaffolds with prophylactic and
therapeutic in vivo efficacy. Specifically, the project will improve lead prototypes through iterative
multi-parameter medicinal chemistry optimization, guided by ADME/PK assessment, cell culture
and mechanistic studies (Research Project 3) and in vivo assessments (Research Project 2) for
exposure, optimum dosing and safety in higher order species (i.e., rats and non-human primates).
The project will manage all synthetic chemistry needs including medicinal chemistry, non-GMP
scaling and validation of analogs, point of compound distribution to CEEAT labs, and
implementation of process manufacturing improvements prior to CRO engagement for API
synthesis to advanced GLP toxicological studies. Additionally, formulation and stability analyses
will be conducted, in collaboration with the UW-Madison Zeeh Formulation Station. Several
activities pertaining to API and formulation generation and characterization will be accompanied
by appropriate certification and analyses in accord with pre-IND requirements, coordinated and
overseen by product development and regulatory consultants within the CEEAT structure.

## Key facts

- **NIH application ID:** 10359714
- **Project number:** 5U19AI142762-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Jennifer E. Golden
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $583,618
- **Award type:** 5
- **Project period:** 2019-03-06 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359714

## Citation

> US National Institutes of Health, RePORTER application 10359714, Medicinal Chemistry Optimization of Anti-Alphaviral Leads and Elucidation of Target and Off Target Engagement (5U19AI142762-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10359714. Licensed CC0.

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