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Targeting polyamines to suppress SARS-CoV-2 related disease

Award Number: UG3TR003597
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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Targeting polyamines to suppress SARS-CoV-2 related disease - ABSTRACT The pandemic COronaVIrus disease 2019 (COVID-19) is an infectious disease, which is caused by a novel and highly pathogenic virus strain SARS-CoV-2 (Severe acute respiratory virus syndrome coronavirus 2). The infection may cause severe lower respiratory tract infection with acute respiratory distress and extrapulmonary organ disfunctions in infected individuals. Treatment strategy that both limits SARS-CoV-2 replication and reduce inflammation associated with COVID-19 would provide the greatest therapeutic benefit. Polyamines are naturally occurring organic cations that are essential for growth and development of both prokaryotic and eukaryotic cells. Many viruses require host polyamines for replication in the infected cells and targeting polyamine metabolism during viral infection showed promising results in in vitro and in vivo animal studies. The goal of this proposal is to test the applicability of two currently FDA approved drugs, eflornithine (other name α-difluoromethylornithine or DFMO) and sulindac, and their combination for prevention or treatment of COVID-19 disease. Eftornithine is an irreversible inhibitor of a key polyamine biosynthetic enzyme ornithine decarboxylase (ODC). Sulindac is a common non-steroidal anti-inflammatory drug (NSAIDs), which also induces polyamine catabolism. Eflornithine and sulindac work in a complementary manner to reduce intracellular polyamine levels. The safety doses of eflornithine/sulindac combination have been established for prevention of recurrence of high-risk adenomas (ClinicalTrials.gov Identifier NCT00118365). In this proposal we will test the hypothesis that eflornithine and sulindac combination will reduce both the intracellular polyamine availability for coronavirus replication, and inflammation associated with COVID-19. We will test this hypothesis using cell culture models (Specific Aim 1) and mouse models of COVID-19 disease (Specific Aim 2). Planning activities in preparation for clinical trials for eflornithine/sulindac combination for antiviral indication in collaboration with Cancer Prevention Pharmaceuticals (CPP) (www.canprevent.com) are also included. The translational goal of this project is to develop the effective approach for prevention COVID-19 infection as well as decreasing severity of the viral infection in the COVID-19 patients. It is essential to develop new approaches to prevention and treatment of virus outbreaks.


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 = -$77,732 )
2024	2022	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	National Center for Advancing Translational Sciences	000	2	10/17/2023	NON-COMPETING CONTINUATION	-$77,732
														Subtotal = -$77,732

Issue Date FY: 2022 ( Subtotal = $306,997 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	National Center for Advancing Translational Sciences	000	2	1/22/2022	NON-COMPETING CONTINUATION	$276,297
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	National Center for Advancing Translational Sciences	001	2	6/9/2022	NON-COMPETING CONTINUATION	$30,700
														Subtotal = $306,997

Issue Date FY: 2021 ( Subtotal = $306,997 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	National Center for Advancing Translational Sciences	000	1	12/17/2020	NEW	$306,997
														Subtotal = $306,997

Grand Total All Awards = $536,262

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Targeting polyamines to suppress SARS-CoV-2 related disease

Award Number: UG3TR003597

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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