Screening of the Pandemic Response Box identifies anti-microsporidia compounds.
Microsporidia are fungal obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to humans and agricultural animals, few drugs are available for the treatment and control of microsporidia. To identify novel inhibitors...
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ftdoajarticles:oai:doaj.org/article:64eb2a97dce14a8c8cee3a485205e96c 2024-02-04T09:58:23+01:00 Screening of the Pandemic Response Box identifies anti-microsporidia compounds. Qingyuan Huang Jie Chen Guoqing Pan Aaron W Reinke 2023-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011806 https://doaj.org/article/64eb2a97dce14a8c8cee3a485205e96c EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0011806 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011806 https://doaj.org/article/64eb2a97dce14a8c8cee3a485205e96c PLoS Neglected Tropical Diseases, Vol 17, Iss 12, p e0011806 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011806 2024-01-07T01:41:23Z Microsporidia are fungal obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to humans and agricultural animals, few drugs are available for the treatment and control of microsporidia. To identify novel inhibitors, we took advantage of the model organism Caenorhabditis elegans infected with its natural microsporidian Nematocida parisii. We used this system to screen the Pandemic Response Box, a collection of 400 diverse compounds with known antimicrobial activity. After testing these compounds in a 96-well format at high (100 μM) and low (40 μM) concentrations, we identified four inhibitors that restored the ability of C. elegans to produce progeny in the presence of N. parisii. All four compounds reduced the pathogen load of both N. parisii and Pancytospora epiphaga, a C. elegans-infecting microsporidia related to human-infecting species. One of these compounds, a known inhibitor of a viral protease, MMV1006203, inhibited invasion and prevented the firing of spores. A bis-indole derivative, MMV1593539, decreased spore viability. An albendazole analog, MMV1782387, inhibited proliferation of N. parisii. We tested albendazole as well as 5 other analogs and observed that MMV1782387 was amongst the strongest inhibitors of N. parisii and displayed the least host toxicity. Our study further demonstrates the effectiveness of the C. elegans-N. parisii system for discovering microsporidia inhibitors and the compounds we identified provide potential scaffolds for anti-microsporidia drug development. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 12 e0011806 |
institution |
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 Qingyuan Huang Jie Chen Guoqing Pan Aaron W Reinke Screening of the Pandemic Response Box identifies anti-microsporidia compounds. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Microsporidia are fungal obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to humans and agricultural animals, few drugs are available for the treatment and control of microsporidia. To identify novel inhibitors, we took advantage of the model organism Caenorhabditis elegans infected with its natural microsporidian Nematocida parisii. We used this system to screen the Pandemic Response Box, a collection of 400 diverse compounds with known antimicrobial activity. After testing these compounds in a 96-well format at high (100 μM) and low (40 μM) concentrations, we identified four inhibitors that restored the ability of C. elegans to produce progeny in the presence of N. parisii. All four compounds reduced the pathogen load of both N. parisii and Pancytospora epiphaga, a C. elegans-infecting microsporidia related to human-infecting species. One of these compounds, a known inhibitor of a viral protease, MMV1006203, inhibited invasion and prevented the firing of spores. A bis-indole derivative, MMV1593539, decreased spore viability. An albendazole analog, MMV1782387, inhibited proliferation of N. parisii. We tested albendazole as well as 5 other analogs and observed that MMV1782387 was amongst the strongest inhibitors of N. parisii and displayed the least host toxicity. Our study further demonstrates the effectiveness of the C. elegans-N. parisii system for discovering microsporidia inhibitors and the compounds we identified provide potential scaffolds for anti-microsporidia drug development. |
format |
Article in Journal/Newspaper |
author |
Qingyuan Huang Jie Chen Guoqing Pan Aaron W Reinke |
author_facet |
Qingyuan Huang Jie Chen Guoqing Pan Aaron W Reinke |
author_sort |
Qingyuan Huang |
title |
Screening of the Pandemic Response Box identifies anti-microsporidia compounds. |
title_short |
Screening of the Pandemic Response Box identifies anti-microsporidia compounds. |
title_full |
Screening of the Pandemic Response Box identifies anti-microsporidia compounds. |
title_fullStr |
Screening of the Pandemic Response Box identifies anti-microsporidia compounds. |
title_full_unstemmed |
Screening of the Pandemic Response Box identifies anti-microsporidia compounds. |
title_sort |
screening of the pandemic response box identifies anti-microsporidia compounds. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011806 https://doaj.org/article/64eb2a97dce14a8c8cee3a485205e96c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 12, p e0011806 (2023) |
op_relation |
https://doi.org/10.1371/journal.pntd.0011806 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011806 https://doaj.org/article/64eb2a97dce14a8c8cee3a485205e96c |
op_doi |
https://doi.org/10.1371/journal.pntd.0011806 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
17 |
container_issue |
12 |
container_start_page |
e0011806 |
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