Repurposing Pyramax®, quinacrine and tilorone as treatments for Ebola virus disease
Copyright © 2020 Elsevier B.V. All rights reserved..
We have recently identified three molecules (tilorone, quinacrine and pyronaridine tetraphosphate) which all demonstrated efficacy in the mouse model of infection with mouse-adapted Ebola virus (EBOV) model of disease and had similar in vitro inhibition of an Ebola pseudovirus (VSV-EBOV-GP), suggesting they interfere with viral entry. Using a machine learning model to predict lysosomotropism these compounds were evaluated for their ability to possess a lysosomotropic mechanism in vitro. We now demonstrate in vitro that pyronaridine tetraphosphate is an inhibitor of Lysotracker accumulation in lysosomes (IC50 = 0.56 μM). Further, we evaluated antiviral synergy between pyronaridine and artesunate (Pyramax®), which are used in combination to treat malaria. Artesunate was not found to have lysosomotropic activity in vitro and the combination effect on EBOV inhibition was shown to be additive. Pyramax® may represent a unique example of the repurposing of a combination product for another disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:182 |
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| Enthalten in: |
Antiviral research - 182(2020) vom: 01. Okt., Seite 104908 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lane, Thomas R [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.07.2021 Date Revised 12.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.antiviral.2020.104908 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313732264 |
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| 100 | 1 | |a Lane, Thomas R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Repurposing Pyramax®, quinacrine and tilorone as treatments for Ebola virus disease |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Revised 12.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a We have recently identified three molecules (tilorone, quinacrine and pyronaridine tetraphosphate) which all demonstrated efficacy in the mouse model of infection with mouse-adapted Ebola virus (EBOV) model of disease and had similar in vitro inhibition of an Ebola pseudovirus (VSV-EBOV-GP), suggesting they interfere with viral entry. Using a machine learning model to predict lysosomotropism these compounds were evaluated for their ability to possess a lysosomotropic mechanism in vitro. We now demonstrate in vitro that pyronaridine tetraphosphate is an inhibitor of Lysotracker accumulation in lysosomes (IC50 = 0.56 μM). Further, we evaluated antiviral synergy between pyronaridine and artesunate (Pyramax®), which are used in combination to treat malaria. Artesunate was not found to have lysosomotropic activity in vitro and the combination effect on EBOV inhibition was shown to be additive. Pyramax® may represent a unique example of the repurposing of a combination product for another disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Antiviral | |
| 650 | 4 | |a Ebola | |
| 650 | 4 | |a Lysosomotropic | |
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| 650 | 7 | |a Drug Combinations |2 NLM | |
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| 700 | 1 | |a Dyall, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Mercer, Luke |e verfasserin |4 aut | |
| 700 | 1 | |a Goodin, Caleb |e verfasserin |4 aut | |
| 700 | 1 | |a Foil, Daniel H |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Huanying |e verfasserin |4 aut | |
| 700 | 1 | |a Postnikova, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Janie Y |e verfasserin |4 aut | |
| 700 | 1 | |a Holbrook, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Madrid, Peter B |e verfasserin |4 aut | |
| 700 | 1 | |a Ekins, Sean |e verfasserin |4 aut | |
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