# In Vitro Evaluation and Characterization of Novel Lead Therapeutic Candidates for Encephalitic Alphavirus Treatment

> **NIH NIH U19** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $489,811

## Abstract

Program Abstract- Project 3
Encephalitic alphaviruses (i.e., Venezuelan, Western, and Eastern Equine Encephalitis viruses) can cause
devastating encephalitis in humans and equids. Several drug discovery efforts have been pursued to fulfill the
unmet needs for effective antivirals for these viruses; however, they are still not available for treatment. Here we
propose the development of a therapeutic candidate for encephalitic alphaviruses based on our two novel lead
series. Prototypes within each series showed potent antiviral activity in vitro and in vivo without adverse effects.
In Aim 1, we will evaluate newly designed compounds in vitro for their potentials as anti-VEEV, EEEV
therapeutics to support the lead optimization of Research Project 1 and contribute to the selection of leads to be
tested in vivo in Research Project 2. In Aim 2, we will contribute to experimental studies and documentation for
the Non-Clinical Virology Study Report for the selected lead candidate in preparation for the informal and Pre-
IND meetings in collaboration with Leidos. We will experimentally establish that the alphaviral RNA replicase is
the target of the lead candidate compounds, using in vitro viral RNA synthesis assays. Specifically, we will
evaluate the anti-V/W/EEEV activity in biologically relevant systems, and importantly, measure the Inhibitory
Quotient to demonstrate antiviral activity in human blood. We will also determine the in vitro safety and
therapeutic index of the lead candidate compounds and define the resistance threshold of resistant viruses.

## Key facts

- **NIH application ID:** 9886199
- **Project number:** 5U19AI142762-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Donghoon Chung
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $489,811
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886199

## Citation

> US National Institutes of Health, RePORTER application 9886199, In Vitro Evaluation and Characterization of Novel Lead Therapeutic Candidates for Encephalitic Alphavirus Treatment (5U19AI142762-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9886199. Licensed CC0.

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