# Novel antifungal agents against coccidioidomycosis

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2024 · $747,858

## Abstract

PROJECT SUMMARY. Fungal infections caused by dimorphic fungi Coccidioides immitis and Coccidioides
posadasii are endemic to the southwestern parts of the United States and the selected areas in the Western
Hemisphere. While most infections are mild and, symptomatic pneumonia can be extremely difficult to treat and
requires lifelong azole therapy underscoring the need for new therapeutic options. In this respect, targeting the
high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway, and, specifically, hybrid
histidine kinases (HHKs), represents a promising approach because HHKs are not present in humans but are
critical components of cellular responses to oxidative stress in pathogenic fungi. We have identified a natural
product candidate that shows potent fungicidal activity against Coccidioides in a murine model. The overarching
goal of this collaborative project is to optimize antifungal activity of synthetic analogs as a potential lead for valley
fever treatment. In Aim 1, we will perform rational SAR study on a lead candidate by introducing modifications in
three distinct parts of the molecule. In Aim 2, we will study the mechanism of action of the lead candidates and
fine-tune in silico model to guide rational analog preparation. In Aim 3, we will perform PK/PD studies and validate
the activity of the optimized candidate in a murine model of coccidioidomycosis. Collectively, this study will result
in a small molecule fungicide with optimized properties for future pre-clinical work.

## Key facts

- **NIH application ID:** 10803632
- **Project number:** 1R01AI175635-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Maciej Walczak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,858
- **Award type:** 1
- **Project period:** 2024-07-17 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803632

## Citation

> US National Institutes of Health, RePORTER application 10803632, Novel antifungal agents against coccidioidomycosis (1R01AI175635-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10803632. Licensed CC0.

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