Targeting polyamines to suppress SARS-CoV-2 related disease

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Principal Investigator: Christian  Bime
Organization: UNIVERSITY OF ARIZONA
Fiscal Year: 2023
Award: $153,040
Funding agency: National Center for Advancing Translational Sciences

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.

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