Open Access
Open access
volume 13 issue 11 pages e0007890

Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection

Thomas R Lane 1
Christopher Massey 2
Jason E. Comer 3
Manu Anantpadma 4
Joel S Freundlich 5
Robert A Davey 4
Peter B Madrid 6
Publication typeJournal Article
Publication date2019-11-21
scimago Q1
wos Q1
SJR1.370
CiteScore7.0
Impact factor3.4
ISSN19352727, 19352735
Infectious Diseases
Public Health, Environmental and Occupational Health
Abstract
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.
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GOST |
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GOST Copy
Lane T. R. et al. Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection // PLoS Neglected Tropical Diseases. 2019. Vol. 13. No. 11. p. e0007890.
GOST all authors (up to 50) Copy
Lane T. R., Massey C., Comer J. E., Anantpadma M., Freundlich J. S., Davey R. A., Madrid P. B., Ekins S. Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection // PLoS Neglected Tropical Diseases. 2019. Vol. 13. No. 11. p. e0007890.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1371/journal.pntd.0007890
UR - https://doi.org/10.1371/journal.pntd.0007890
TI - Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection
T2 - PLoS Neglected Tropical Diseases
AU - Lane, Thomas R
AU - Massey, Christopher
AU - Comer, Jason E.
AU - Anantpadma, Manu
AU - Freundlich, Joel S
AU - Davey, Robert A
AU - Madrid, Peter B
AU - Ekins, Sean
PY - 2019
DA - 2019/11/21
PB - Public Library of Science (PLoS)
SP - e0007890
IS - 11
VL - 13
PMID - 31751347
SN - 1935-2727
SN - 1935-2735
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2019_Lane,
author = {Thomas R Lane and Christopher Massey and Jason E. Comer and Manu Anantpadma and Joel S Freundlich and Robert A Davey and Peter B Madrid and Sean Ekins},
title = {Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection},
journal = {PLoS Neglected Tropical Diseases},
year = {2019},
volume = {13},
publisher = {Public Library of Science (PLoS)},
month = {nov},
url = {https://doi.org/10.1371/journal.pntd.0007890},
number = {11},
pages = {e0007890},
doi = {10.1371/journal.pntd.0007890}
}
MLA
Cite this
MLA Copy
Lane, Thomas R., et al. “Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection.” PLoS Neglected Tropical Diseases, vol. 13, no. 11, Nov. 2019, p. e0007890. https://doi.org/10.1371/journal.pntd.0007890.
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