# Autophagy Modulators as Novel Broad-Spectrum Anti-Infective Agents

> **NIH NIH U19** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $7,381,267

## Abstract

Program Summary – Overview: The goal of this Center of Excellence for Translational Research
(CETR) Program is to develop host-directed broad-spectrum anti-infective agents against NIAID
priority pathogens by targeting the autophagy pathway. The most common approach for treating infectious
diseases is to target pathogen-encoded proteins. However, pathogens can evolve resistance, and the
spectrum of many clinically used anti-infective agents is restricted to taxonomically-related organisms. The use
of host-directed anti-infective therapies offers several potential advantages to treating infectious diseases;
including (1) the ability to target taxonomically-diverse pathogens; (2) decreased potential for promoting the
emergence of drug-resistant organisms; and (3) the possibility of developing single compounds that target
multiple pathogens, thereby decreasing the financial and regulatory barriers for developing anti-infective
agents. Moreover, broad-spectrum host-directed therapeutics, once approved for clinical use against more
common agents (in which clinical trials are feasible), can be deployed for emerging pathogens, new outbreaks,
and pathogens engineered with ill intent. Proof-of-principle of this approach – namely, the development of
effective host-directed broad-spectrum anti-infective therapeutics – could have a dramatic impact on
how we treat and prevent infectious diseases. In recent years, extensive data have emerged (from our
group of CETR investigators and others) indicating that degradative autophagy and autophagy-related (ATG)
gene-dependent functions in immunity are crucial in host defense against taxonomically diverse pathogens.
Furthermore, we and others showed that autophagy augmentation is safe and beneficial in animal models of
infectious diseases. Therefore, the development of compounds that enhance autophagy and ATG gene-
dependent immunity represents an attractive strategy for host-directed broad-spectrum anti-infective
therapeutics. This new application has evolved from a currently funded, highly successful CETR Program
entitled “Autophagy Modulators as Novel Broad-Spectrum Anti-Infective Agents”. The goal of both the currently
funded Program and this new proposal is to generate autophagy pathway-directed compounds that are active
against a range of taxonomically-unrelated pathogens (selected based on priority status and medical need). To
accomplish our goals, we will pursue a strategy that advances our current therapeutic leads and validates new
targets to expand our discovery pipeline. We will accomplish our goals through five research projects entitled:
RP1: Targeting Beclin 1 complexes for broad-spectrum anti-infective therapeutics.
RP2: Targeting genes and pathways for autophagy-dependent inhibition of bacterial infection.
RP3: Targeting Atg gene-dependent immunity for novel anti-infective therapeutics.
RP4: Harnessing autophagy to treat tuberculosis.
RP5: Chemical proteomic discovery of small-molecule probes for aut...

## Key facts

- **NIH application ID:** 9893808
- **Project number:** 5U19AI142784-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** HERBERT W VIRGIN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $7,381,267
- **Award type:** 5
- **Project period:** 2019-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893808

## Citation

> US National Institutes of Health, RePORTER application 9893808, Autophagy Modulators as Novel Broad-Spectrum Anti-Infective Agents (5U19AI142784-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893808. Licensed CC0.

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