Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
12
07
2019
accepted:
29
10
2019
revised:
05
12
2019
pubmed:
22
11
2019
medline:
19
2
2020
entrez:
22
11
2019
Statut:
epublish
Résumé
Recent outbreaks of the Ebola virus (EBOV) have focused attention on the dire need for antivirals to treat these patients. We identified pyronaridine tetraphosphate as a potential candidate as it is an approved drug in the European Union which is currently used in combination with artesunate as a treatment for malaria (EC50 between 420 nM-1.14 μM against EBOV in HeLa cells). Range-finding studies in mice directed us to a single 75 mg/kg i.p. dose 1 hr after infection which resulted in 100% survival and statistically significantly reduced viremia at study day 3 from a lethal challenge with mouse-adapted EBOV (maEBOV). Further, an EBOV window study suggested we could dose pyronaridine 2 or 24 hrs post-exposure to result in similar efficacy. Analysis of cytokine and chemokine panels suggests that pyronaridine may act as an immunomodulator during an EBOV infection. Our studies with pyronaridine clearly demonstrate potential utility for its repurposing as an antiviral against EBOV and merits further study in larger animal models with the added benefit of already being used as a treatment against malaria.
Identifiants
pubmed: 31751347
doi: 10.1371/journal.pntd.0007890
pii: PNTD-D-19-01137
pmc: PMC6894882
doi:
Substances chimiques
Antimalarials
0
Antiviral Agents
0
Cytokines
0
Naphthyridines
0
pyronaridine
TD3P7Q3SG6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0007890Subventions
Organisme : NCATS NIH HHS
ID : R21 TR001718
Pays : United States
Déclaration de conflit d'intérêts
SE is CEO of Collaborations Pharmaceuticals, Inc. TRL is an employee at Collaborations Pharmaceuticals, Inc.
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