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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-11-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0007890 |
| _version_ | 1818726312290811904 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T21:56:12Z |
| format | Article |
| id | doaj.art-848b3e0787cd4db1b567389b6f045122 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-17T21:56:12Z |
| publishDate | 2019-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-848b3e0787cd4db1b567389b6f0451222022-12-21T21:31:07ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352019-11-011311e000789010.1371/journal.pntd.0007890Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection.Thomas R LaneChristopher MasseyJason E ComerManu AnantpadmaJoel S FreundlichRobert A DaveyPeter B MadridSean EkinsRecent 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.https://doi.org/10.1371/journal.pntd.0007890 |
| spellingShingle | 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. PLoS Neglected Tropical Diseases |
| title | 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_short | Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. |
| title_sort | repurposing the antimalarial pyronaridine tetraphosphate to protect against ebola virus infection |
| url | https://doi.org/10.1371/journal.pntd.0007890 |
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