# Development of Dual Efficacy Therapeutic Against Cryptosporidiosis and Giardiasis

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $257,125

## Abstract

Project Summary/Abstract
The potential for devastating consequences of cryptosporidiosis or giardiasis diarrhea in immunocompromised
patients and malnourished children emphasizes the need for an effective therapy that could be used
syndromically as a single agent appropriate for administration where diagnosis may be delayed or uncertain.
This is also true for asymptomatic presentations of both diseases that can be devastating. The etiologic
parasites colonize and reproduce in the small intestines of mammalian hosts where they are associated with
microvilli of the epithelial cells. Hence, potential for finding dual therapeutic is high based on common
anatomical site of infection. Protein kinase inhibitors have attracted considerable attention as potential
therapeutics since a number of them have been released as drugs in recent years and many are in various
phases of clinical trials. In a semi High throughput screening of MMV Pathogen box, we demonstrated that
dual hitting molecules including kinase inhibitors with no obvious chemical similarity with any previously
characterized anti-parasite drugs offer new medicinal chemistry opportunities for development of effective
multi-parasite therapeutics against cryptosporidiosis and giardiasis. This research proposal capitalizes on the
unique preliminary findings to hypothesize that effective single agent therapy that could be used syndromically
for treatment of either cryptosporidiosis or giardiasis is possible. In Years 1-2 (R21 phase): we will screen for,
select and optimize dual effective hits to early leads. In Specific Aim 1a – we will determine in vitro efficacy of
~2000 unique chemical scaffold inhibitor clusters in blocking parasites growth using direct phenotypic
screening. We will select up to 50 hit scaffolds by rank order of efficacy against parasites and potential for
mammalian cytotoxicity. In Specific Aim 1b – we will screen analogs of each of the 50 hit scaffolds identified
in Aim 1a to develop structural activity relationship. Criteria for moving forward will include parasite killing
efficiency, either static vs. cidal, selectivity, and ease of medicinal chemistry development. In Specific Aim 2
we will use stability in simulated gastric/intestinal fluids, pharmacologic and pharmacokinetic studies to identify
~20 effective early lead for both species and confirm clinical efficacy in mouse infection models. In Years 3-5
(R33 phase): We will do lead optimization for efficacy, selectivity, and PK/ADMET properties under Specific
Aim 3 - Medicinal chemistry; pharmacokinetic studies, in vitro compound efficacy, pharmacology, toxicity and
resistance. In the final part of the project under Specific Aim 4 - In vivo compound efficacy and resistance,
optimized leads will be evaluated for clinical efficacy in the mouse infection models and determine potential
ease of developing acquired resistance and fitness cost of resistance to compounds being investigated. The
product of this research study wou...

## Key facts

- **NIH application ID:** 9851345
- **Project number:** 5R21AI140881-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kayode K Ojo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $257,125
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851345

## Citation

> US National Institutes of Health, RePORTER application 9851345, Development of Dual Efficacy Therapeutic Against Cryptosporidiosis and Giardiasis (5R21AI140881-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851345. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*