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Development of a Novel Inhibitor of Ricin: A Potential Therapeutic Lead against Deadly Shiga and Related Toxins

Award Number: R15AI124044
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: 01/02/2017
PERIOD OF PERFORMANCE END DATE: 12/31/2019

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Development of a Novel Inhibitor of Ricin: A Potential Therapeutic Lead against Deadly Shiga and Related Toxins - Abstract The PI proposes a high-impact collaborative research project to develop new inhibitors for ribosome inactivating proteins (RIPs), such as ricin and Shiga toxin. Ricin toxin, produced by the castor bean plant, has a nefarious past. Ricin is a well-known homicidal poison and has been used in several bioterrorist attacks. Shiga toxin is a deadly product of enterobacterial Escherichia coli. RIPs are RNA N-glycosidases that enzymatically remove specific purine residues from the universally conserved sarcin/ricin loop (S/R loop) of large ribosomal RNA, causing cellular death. There are no effective pharmaceuticals for either ricin or Shiga toxin poisoning. The PI proposes using a viral protein (VPg) from turnip mosaic virus that we have shown to inhibit ricin activity in vitro. The goals of this proposal are: 1) Establish conditions for VPg-ricin complex formation and the rates of VPg-ricin interactions; 2) Determine minimum VPg peptide that effectively inhibits ricin and Shiga toxins; and 3) Optimize conditions to enhance inhibition of these toxic proteins. This is an innovative activity. Based on the structural and mechanistic similarities of these toxins and previously acquired data showing that VPg peptides inhibit ricin activity in vitro, we believe the outcomes of this activity will provide leads for the synthesis of therapeutic peptides. In turn, this will serve as a catalyst for the development of constructively applied solutions for the inhibition of these deadly toxins. Furthermore, this proposal will enhance the infrastructure of research and education at John Jay College, introducing biochemical and biomedical research experiences to underrepresented minority and female students, who would otherwise lack such opportunities. This would allow them to experience a broad spectrum of techniques, and acquire skills such as data analysis used in modern scientific investigations, while developing a vast network of partnerships among scientists from national and international institutions.


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: 2020 ( Subtotal = -$4 )
2020	2017	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	5/19/2020	NEW	-$4
														Subtotal = -$4

Issue Date FY: 2017 ( Subtotal = $445,387 )
2017	2017	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	1/2/2017	NEW	$445,387
														Subtotal = $445,387

Grand Total All Awards = $445,383

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Development of a Novel Inhibitor of Ricin: A Potential Therapeutic Lead against Deadly Shiga and Related Toxins

Award Number: R15AI124044

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: 01/02/2017

PERIOD OF PERFORMANCE END DATE: 12/31/2019

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