# Identifying the Target of a Potent and Selective Inhibitor of Babesia Blood Stages.

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $254,250

## Abstract

Project Summary
Tick-borne diseases, including human babesiosis, are on the rise. Caused by protozoa in the genus Babesia,
this infection can be life-threatening in asplenic or immunocompromised individuals. Based on the most recent
CDC data, the number of annual reported cases in the US nearly doubled between 2011 and 2018, with some
states experiencing a greater than 10-fold increase. Treatment options for babesiosis in immunocompromised
individuals are very limited, have substantial side effects, and often fail to fully clear the parasites. This makes
the development of new treatments imperative. We recently developed the small molecule inhibitor C10 that has
low toxicity and excellent activity against multiple species of Babesia parasites that infect humans. The molecular
target of this inhibitor is clearly druggable, essential, and likely novel but is currently unknown. Using a
combination of genetic and biochemical approaches, the proposed experiments will identify and validate the
parasite target of this inhibitor. In AIM1 we will identify what parasite proteins that bind tightly to C10 using µMap,
a newly developed photocatalytic chemo-proteomics platform with greatly enhanced sensitivity and specificity
over current methods. In a parallel effort, we have selected multiple independent parasite lines with partial
resistance to C10. Since mutation in genes encoding a drug target is the most common resistance mechanism,
AIM2 will use whole-genome resequencing to identify genes with newly acquired mutations in resistant lines but
absent from the susceptible parent to identify an additional set of target candidates. Finally, we will validate target
candidates from AIM1 and AIM2 by confirming that engineered mutations of the target, such as knockdown or
overexpression, alters susceptibility to C10. If feasible, we will also test if C10 binds to and inhibits the activity of
the recombinantly expressed target. Throughout these experiments will use C13, a nearly identical but inactive
isomer of C10, to ensure target specificity.

## Key facts

- **NIH application ID:** 10527782
- **Project number:** 1R21AI166436-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Bjorn Felix Caesar Kafsack
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2022-07-07 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527782

## Citation

> US National Institutes of Health, RePORTER application 10527782, Identifying the Target of a Potent and Selective Inhibitor of Babesia Blood Stages. (1R21AI166436-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10527782. Licensed CC0.

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