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Therapeutic Repurposing for Human Babesiosis: Leveraging a High-Throughput Screen of Drugs and Clinical-Stage Compounds

Award Number: R21AI196865
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/11/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Therapeutic Repurposing for Human Babesiosis: Leveraging a High-Throughput Screen of Drugs and Clinical-Stage Compounds - Project Summary Babesiosis is a malaria-like disease resulting from infection of humans by microbial parasites of the Babesia species. Infections are transmitted through tick bites and frequently co-occur with Lyme Disease, exacerbating symptoms. Immunocompromised individuals are most vulnerable to severe disease. The number of babesiosis cases in the United States, caused primarily by Babesia microti, have more than doubled over the past 15 years. There is no vaccine for babesiosis and drug treatment options are few, with medicines exhibiting poor efficacy and vulnerability to disease relapse with resistant parasites. During drug development, one of the most common reasons for rejection of lead candidates is the discovery of toxicity during animal or human trials. Repurposing a drug for a disease addresses this liability by utilizing compounds already validated for safety in development for other medical conditions. The few existing drugs for human babesiosis have been repurposed from other infectious diseases, in particular malaria. This approach relying on drug development from similar diseases, while addressing toxicity, is limited in its survey of chemical- sensitivity of babesiosis parasites that could be exploited for treatment. Furthermore, there are no accessible culture models for B. microti, presenting a challenge to searches for new, medically relevant antibabesials. For an unbiased search for new antibabesial molecules, we recently carried out a primary chemical screen for inhibitors of proliferation of Babesia divergens, a cow- and human-infecting babesiosis parasite that grows readily in the lab. Critically, in our ~6800 compound screen we tested most FDA-approved drugs and compounds in clinical development, identifying hundreds of small molecules that suppress proliferation that have already undergone some safety testing in humans. These preliminary data provide an unprecedented resource to discover small molecules for repurposing for human babesiosis, to be pursued as follows: Aim 1. Identify potent and broad-spectrum antibabesial inhibitors from a repurposing collection Aim 2. Rapidly identify compounds that present a high barrier to antibabesial resistance Aim 3. Identify compounds that suppress Babesia microti in a mouse model of infection Our screen of a comprehensive library of advanced clinical compounds covering infectious and non-infectious diseases substantially expands the scope of potential drug repurposing for human babesiosis. By building in pan-Babesia species activity and assessment of drug resistance liability early in the process, we expect to generate a short list of small molecule candidates that addresses shortcomings of existing therapies for babesiosis. The tools and strategy we develop here may well help catalyze future drug development for the disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $228,000 )
2026	2026	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	1	8/11/2026	NEW	$228,000
														Subtotal = $228,000

Grand Total All Awards = $228,000

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Therapeutic Repurposing for Human Babesiosis: Leveraging a High-Throughput Screen of Drugs and Clinical-Stage Compounds

Award Number: R21AI196865

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/11/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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