Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection.
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 tr...
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ftdoajarticles:oai:doaj.org/article:848b3e0787cd4db1b567389b6f045122 2023-05-15T15:06:36+02:00 Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. Thomas R Lane Christopher Massey Jason E Comer Manu Anantpadma Joel S Freundlich Robert A Davey Peter B Madrid Sean Ekins 2019-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007890 https://doaj.org/article/848b3e0787cd4db1b567389b6f045122 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007890 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007890 https://doaj.org/article/848b3e0787cd4db1b567389b6f045122 PLoS Neglected Tropical Diseases, Vol 13, Iss 11, p e0007890 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007890 2022-12-31T07:48:36Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 11 e0007890 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Thomas R Lane Christopher Massey Jason E Comer Manu Anantpadma Joel S Freundlich Robert A Davey Peter B Madrid Sean Ekins Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Thomas R Lane Christopher Massey Jason E Comer Manu Anantpadma Joel S Freundlich Robert A Davey Peter B Madrid Sean Ekins |
author_facet |
Thomas R Lane Christopher Massey Jason E Comer Manu Anantpadma Joel S Freundlich Robert A Davey Peter B Madrid Sean Ekins |
author_sort |
Thomas R Lane |
title |
Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. |
title_short |
Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. |
title_full |
Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. |
title_fullStr |
Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. |
title_full_unstemmed |
Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. |
title_sort |
repurposing the antimalarial pyronaridine tetraphosphate to protect against ebola virus infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007890 https://doaj.org/article/848b3e0787cd4db1b567389b6f045122 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 11, p e0007890 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007890 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007890 https://doaj.org/article/848b3e0787cd4db1b567389b6f045122 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007890 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
11 |
container_start_page |
e0007890 |
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1766338171534049280 |