Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.

A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Wei Sun, Yoon-Dong Park, Janyce A Sugui, Annette Fothergill, Noel Southall, Paul Shinn, John C McKew, Kyung J Kwon-Chung, Wei Zheng, Peter R Williamson
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
Materias:
R
Q
Acceso en línea:https://doaj.org/article/6df2c262060b48b5a5bb9950eb518e88
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:6df2c262060b48b5a5bb9950eb518e88
record_format dspace
spelling oai:doaj.org-article:6df2c262060b48b5a5bb9950eb518e882021-11-18T08:58:39ZRapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.1932-620310.1371/journal.pone.0070506https://doaj.org/article/6df2c262060b48b5a5bb9950eb518e882013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23990907/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.Wei SunYoon-Dong ParkJanyce A SuguiAnnette FothergillNoel SouthallPaul ShinnJohn C McKewKyung J Kwon-ChungWei ZhengPeter R WilliamsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70506 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Wei Sun
Yoon-Dong Park
Janyce A Sugui
Annette Fothergill
Noel Southall
Paul Shinn
John C McKew
Kyung J Kwon-Chung
Wei Zheng
Peter R Williamson
Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.
description A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.
format article
author Wei Sun
Yoon-Dong Park
Janyce A Sugui
Annette Fothergill
Noel Southall
Paul Shinn
John C McKew
Kyung J Kwon-Chung
Wei Zheng
Peter R Williamson
author_facet Wei Sun
Yoon-Dong Park
Janyce A Sugui
Annette Fothergill
Noel Southall
Paul Shinn
John C McKew
Kyung J Kwon-Chung
Wei Zheng
Peter R Williamson
author_sort Wei Sun
title Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.
title_short Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.
title_full Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.
title_fullStr Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.
title_full_unstemmed Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.
title_sort rapid identification of antifungal compounds against exserohilum rostratum using high throughput drug repurposing screens.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/6df2c262060b48b5a5bb9950eb518e88
work_keys_str_mv AT weisun rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT yoondongpark rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT janyceasugui rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT annettefothergill rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT noelsouthall rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT paulshinn rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT johncmckew rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT kyungjkwonchung rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT weizheng rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
AT peterrwilliamson rapididentificationofantifungalcompoundsagainstexserohilumrostratumusinghighthroughputdrugrepurposingscreens
_version_ 1718421087724765184