Repurposing of the antibiotic nitroxoline for the treatment of mpox
© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC..
The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side-effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat-resistant strain and increased the anti-mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co-transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:95 |
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| Enthalten in: |
Journal of medical virology - 95(2023), 3 vom: 10. März, Seite e28652 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bojkova, Denisa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.04.2023 Date Revised 13.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jmv.28652 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM354027050 |
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| 245 | 1 | 0 | |a Repurposing of the antibiotic nitroxoline for the treatment of mpox |
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| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. | ||
| 520 | |a The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side-effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat-resistant strain and increased the anti-mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co-transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity | ||
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| 700 | 1 | |a Tietgen, Manuela |e verfasserin |4 aut | |
| 700 | 1 | |a Steinhorst, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Bechtel, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Rothenburger, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a Kandler, Joshua D |e verfasserin |4 aut | |
| 700 | 1 | |a Schneider, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Corman, Victor M |e verfasserin |4 aut | |
| 700 | 1 | |a Ciesek, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Rabenau, Holger F |e verfasserin |4 aut | |
| 700 | 1 | |a Wass, Mark N |e verfasserin |4 aut | |
| 700 | 1 | |a Kippenberger, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Göttig, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Michaelis, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Cinatl, Jindrich |c Jr |e verfasserin |4 aut | |
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