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Antiparasitic Agent Discovery from Natural Products for the Treatment of a Globally Emerging Disease

Award Number: R21AI178354
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Hawaii leads the nation in reported cases of human angiostrongyliasis, or rat lungworm (RLW) disease, a potentially lethal central nervous system infection caused by the parasitic nematode Angiostrongylus cantonensis. Anthelmintics specifically targeting A. cantonensis are not available. Thus, an urgent need exists to develop effective drugs for this emerging and neglected tropical disease. Natural products are the best source of drug leads for parasitic diseases, as previously demonstrated for parasitic diseases, such as artemisinin for malaria, Ivermectin for river blindness and lymphatic filariasis. Our long-term goal is to identify novel anthelmintic natural products from microorganisms including under-explored Hawaiian fungi and bacteria. The objective of the proposed research is to discover natural products that immobilize infectious third stage A. cantonensis larvae (L3). Our central hypothesis is that natural products such as the under-explored endophytic fungi in Hawaii and other microorganisms are a rich source for anti-A. cantonensis natural product drug discovery. The rationale of the proposed research is that once novel potent anti-RLW natural products are identified, lead compounds will be studied for their mechanisms of action and tested in vivo in the near future. The objectives of this project will be accomplished by two specific aims: (1) Screen NPs against infectious A. cantonensis L3; (2) Identify and characterize motility inhibiting and viability reducing bioactive NPs via assay-guided separation and structure elucidation, and assess Blood-brain barrier (BBB) permeability and efficacy. This study is innovative because it: (a) uses our newly established high-throughput screening (HTS) assay to screen our new and unique natural product library (NPL) against RLW; and (b) utilizes a new infrared-based motility-inhibition bioassay to screen fractions from our NPL against infectious L3 larvae. The proposed project is significant because it aims to reduce human suffering from emerging infectious diseases through the development of effective therapeutics, and will strengthen the research infrastructure for natural product drug discovery and molecular medicine in Hawaii. Our approach could serve as a model for carrying out natural product drug discovery against other newly emerging parasitic diseases. This project will also provide research experience opportunities for graduate students and ethnically diverse and socioeconomically disadvantaged undergraduate students in the state of Hawaii.


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: 2024 ( Subtotal = $181,875 )
2024	2024	UNIVERSITY OF HAWAII	200 W KAWILI ST	HILO	HI	96720	HAWAII	USA	Allergy and Infectious Diseases Research	000	2	6/24/2024	NON-COMPETING CONTINUATION	$181,875
														Subtotal = $181,875

Issue Date FY: 2023 ( Subtotal = $218,250 )
2023	2023	UNIVERSITY OF HAWAII	200 W KAWILI ST	HILO	HI	96720	HAWAII	USA	Allergy and Infectious Diseases Research	000	1	7/11/2023	NEW	$218,250
														Subtotal = $218,250

Grand Total All Awards = $400,125

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Antiparasitic Agent Discovery from Natural Products for the Treatment of a Globally Emerging Disease

Award Number: R21AI178354

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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