# Project 4 - Influenza - UAB

> **NIH NIH U19** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $937,498

## Abstract

SUMMARY
The overall goal of this project is to identify new therapies that target influenza virus replication. The global
health burden of annual influenza infections and periodic epidemics coupled with the emergence of avian
influenza viruses, like H5NX and H7N9, highlight the urgent need for new effective treatments. A primary
concern with the current drugs used to treat influenza in the U.S. is the development of resistance mutations
that negate therapeutic benefit. Both published evidence and clinical experience suggest strongly that targeting
the influenza virus RNA dependent RNA polymerase (RdRp) complex is a rational approach for antiviral
therapy. This complex is responsible for many viral functions, including 5´ cap recognition, endonucleolytic
cleavage, RNA synthesis, and polyadenylation providing multiple functional domains as targets for antiviral
drug therapy and combination therapy. Agents can target the distinct functions and, theoretically, reduce the
minimize development of resistance since resistance mutations would likely reduce the fidelity of the RdRp.
One oral agent targeting the endonuclease domain, baloxavir, has shown efficacy in uncomplicated influenza
and was recently approved in Japan for treating influenza in adults and children. A second oral agent targeting
the 5´ cap binding domain, pimodivir, has shown antiviral activity in uncomplicated influenza and is advancing
in clinical development. A third oral agent, favipiravir, targeting the polymerase activity has been approved in
Japan for treating novel influenza strains not inhibited by neuraminidase inhibitors. We have recently identified
several potent molecules through a collaborative public private partnership that inhibit RdRp functions. This
research team provides the medicinal chemistry expertise, follow up assays, and in vivo experience to
transform active hits into lead compounds and promises to yield new classes of highly active molecules that
target the RdRp complex.

## Key facts

- **NIH application ID:** 10380669
- **Project number:** 5U19AI142759-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** RICHARD J. WHITLEY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $937,498
- **Award type:** 5
- **Project period:** 2019-03-07 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380669

## Citation

> US National Institutes of Health, RePORTER application 10380669, Project 4 - Influenza - UAB (5U19AI142759-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380669. Licensed CC0.

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