Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model
Background: With the expansion of animal production, parasitic helminths are gaining increasing economic importance. However, application of several established deworming agents can harm treated hosts and environment due to their low specificity. Furthermore, the number of parasite strains showing r...
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Online Access: | https://hdl.handle.net/11392/2499916 https://doi.org/10.1186/s12864-022-08882-1 |
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ftunivferrarair:oai:sfera.unife.it:11392/2499916 2024-09-09T19:39:30+00:00 Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model Schmidt, Hanno Mauer, Katharina Glaser, Manuel Dezfuli, Bahram Sayyaf Hellmann, Sören Lukas Silva Gomes, Ana Lúcia Butter, Falk Wade, Rebecca C Hankeln, Thomas Herlyn, Holger Schmidt, Hanno Mauer, Katharina Glaser, Manuel Dezfuli, Bahram Sayyaf Hellmann, Sören Luka Silva Gomes, Ana Lúcia Butter, Falk Wade, Rebecca C Hankeln, Thoma Herlyn, Holger 2022 STAMPA https://hdl.handle.net/11392/2499916 https://doi.org/10.1186/s12864-022-08882-1 eng eng info:eu-repo/semantics/altIdentifier/pmid/36180835 info:eu-repo/semantics/altIdentifier/wos/WOS:000862405100001 volume:23 issue:1 firstpage:677-1 lastpage:677-16 numberofpages:16 journal:BMC GENOMICS https://hdl.handle.net/11392/2499916 doi:10.1186/s12864-022-08882-1 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85139012032 info:eu-repo/semantics/openAccess Active ingredients Virtual ligand screening Anthelmintics Medical genomics Parasites Target molecule info:eu-repo/semantics/article 2022 ftunivferrarair https://doi.org/10.1186/s12864-022-08882-1 2024-06-19T13:22:10Z Background: With the expansion of animal production, parasitic helminths are gaining increasing economic importance. However, application of several established deworming agents can harm treated hosts and environment due to their low specificity. Furthermore, the number of parasite strains showing resistance is growing, while hardly any new anthelminthics are being developed. Here, we present a bioinformatics workflow designed to reduce the time and cost in the development of new strategies against parasites. The workflow includes quantitative transcriptomics and proteomics, 3D structure modeling, binding site prediction, and virtual ligand screening. Its use is demonstrated for Acanthocephala (thorny-headed worms) which are an emerging pest in fish aquaculture. We included three acanthocephalans (Pomphorhynchus laevis, Neoechinorhynchus agilis, Neoechinorhynchus buttnerae) from four fish species (common barbel, European eel, thinlip mullet, tambaqui).Results: The workflow led to eleven highly specific candidate targets in acanthocephalans. The candidate targets showed constant and elevated transcript abundances across definitive and accidental hosts, suggestive of constitutive expression and functional importance. Hence, the impairment of the corresponding proteins should enable specific and effective killing of acanthocephalans. Candidate targets were also highly abundant in the acanthocephalan body wall, through which these gutless parasites take up nutrients. Thus, the candidate targets are likely to be accessible to compounds that are orally administered to fish. Virtual ligand screening led to ten compounds, of which five appeared to be especially promising according to ADMET, GHS, and RO5 criteria: tadalafil, pranazepide, piketoprofen, heliomycin, and the nematicide derquantel.Conclusions: The combination of genomics, transcriptomics, and proteomics led to a broadly applicable procedure for the cost- and time-saving identification of candidate target proteins in parasites. The ligands predicted to bind ... Article in Journal/Newspaper European eel Università degli Studi di Ferrara: CINECA IRIS BMC Genomics 23 1 |
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Open Polar |
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Università degli Studi di Ferrara: CINECA IRIS |
op_collection_id |
ftunivferrarair |
language |
English |
topic |
Active ingredients Virtual ligand screening Anthelmintics Medical genomics Parasites Target molecule |
spellingShingle |
Active ingredients Virtual ligand screening Anthelmintics Medical genomics Parasites Target molecule Schmidt, Hanno Mauer, Katharina Glaser, Manuel Dezfuli, Bahram Sayyaf Hellmann, Sören Lukas Silva Gomes, Ana Lúcia Butter, Falk Wade, Rebecca C Hankeln, Thomas Herlyn, Holger Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model |
topic_facet |
Active ingredients Virtual ligand screening Anthelmintics Medical genomics Parasites Target molecule |
description |
Background: With the expansion of animal production, parasitic helminths are gaining increasing economic importance. However, application of several established deworming agents can harm treated hosts and environment due to their low specificity. Furthermore, the number of parasite strains showing resistance is growing, while hardly any new anthelminthics are being developed. Here, we present a bioinformatics workflow designed to reduce the time and cost in the development of new strategies against parasites. The workflow includes quantitative transcriptomics and proteomics, 3D structure modeling, binding site prediction, and virtual ligand screening. Its use is demonstrated for Acanthocephala (thorny-headed worms) which are an emerging pest in fish aquaculture. We included three acanthocephalans (Pomphorhynchus laevis, Neoechinorhynchus agilis, Neoechinorhynchus buttnerae) from four fish species (common barbel, European eel, thinlip mullet, tambaqui).Results: The workflow led to eleven highly specific candidate targets in acanthocephalans. The candidate targets showed constant and elevated transcript abundances across definitive and accidental hosts, suggestive of constitutive expression and functional importance. Hence, the impairment of the corresponding proteins should enable specific and effective killing of acanthocephalans. Candidate targets were also highly abundant in the acanthocephalan body wall, through which these gutless parasites take up nutrients. Thus, the candidate targets are likely to be accessible to compounds that are orally administered to fish. Virtual ligand screening led to ten compounds, of which five appeared to be especially promising according to ADMET, GHS, and RO5 criteria: tadalafil, pranazepide, piketoprofen, heliomycin, and the nematicide derquantel.Conclusions: The combination of genomics, transcriptomics, and proteomics led to a broadly applicable procedure for the cost- and time-saving identification of candidate target proteins in parasites. The ligands predicted to bind ... |
author2 |
Schmidt, Hanno Mauer, Katharina Glaser, Manuel Dezfuli, Bahram Sayyaf Hellmann, Sören Luka Silva Gomes, Ana Lúcia Butter, Falk Wade, Rebecca C Hankeln, Thoma Herlyn, Holger |
format |
Article in Journal/Newspaper |
author |
Schmidt, Hanno Mauer, Katharina Glaser, Manuel Dezfuli, Bahram Sayyaf Hellmann, Sören Lukas Silva Gomes, Ana Lúcia Butter, Falk Wade, Rebecca C Hankeln, Thomas Herlyn, Holger |
author_facet |
Schmidt, Hanno Mauer, Katharina Glaser, Manuel Dezfuli, Bahram Sayyaf Hellmann, Sören Lukas Silva Gomes, Ana Lúcia Butter, Falk Wade, Rebecca C Hankeln, Thomas Herlyn, Holger |
author_sort |
Schmidt, Hanno |
title |
Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model |
title_short |
Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model |
title_full |
Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model |
title_fullStr |
Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model |
title_full_unstemmed |
Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model |
title_sort |
identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model |
publishDate |
2022 |
url |
https://hdl.handle.net/11392/2499916 https://doi.org/10.1186/s12864-022-08882-1 |
genre |
European eel |
genre_facet |
European eel |
op_relation |
info:eu-repo/semantics/altIdentifier/pmid/36180835 info:eu-repo/semantics/altIdentifier/wos/WOS:000862405100001 volume:23 issue:1 firstpage:677-1 lastpage:677-16 numberofpages:16 journal:BMC GENOMICS https://hdl.handle.net/11392/2499916 doi:10.1186/s12864-022-08882-1 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85139012032 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/s12864-022-08882-1 |
container_title |
BMC Genomics |
container_volume |
23 |
container_issue |
1 |
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1809908619148263424 |