Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.

Drug repurposing is an important strategy in COVID-19 treatment, but many clinically approved compounds have not been extensively studied in the context of embryogenesis, thus limiting their administration during pregnancy. Here we used the zebrafish embryo model organism to test the effects of 162...

ver descrição completa

Detalhes bibliográficos
Autores: Ernst, Alexander, Piragyte, Indre, Mp, Ayisha Marwa, Le, Ngoc Dung, Grandgirard, Denis, Leib, Stephen L, Oates, Andrew, Mercader, Nadia
Tipo de documento: artigo
Data de publicação:2023
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/19341
Acesso em linha:http://hdl.handle.net/20.500.12105/19341
Access Level:Acceso aberto
Palavra-chave:Antiviral Agents
Embryonic Development
Animals
Female
Humans
Pregnancy
COVID-19
COVID-19 Drug Treatment
Ritonavir
SARS-CoV-2
Zebrafish
Embryo, Nonmammalian
id ES_69e7a04fcdc763f4f12bd2c5f4384412
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/19341
network_acronym_str ES
network_name_str España
repository_id_str
spelling Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.Ernst, AlexanderPiragyte, IndreMp, Ayisha MarwaLe, Ngoc DungGrandgirard, DenisLeib, Stephen LOates, AndrewMercader, NadiaAntiviral AgentsEmbryonic DevelopmentAnimalsFemaleHumansPregnancyCOVID-19COVID-19 Drug TreatmentRitonavirSARS-CoV-2ZebrafishEmbryo, NonmammalianDrug repurposing is an important strategy in COVID-19 treatment, but many clinically approved compounds have not been extensively studied in the context of embryogenesis, thus limiting their administration during pregnancy. Here we used the zebrafish embryo model organism to test the effects of 162 marketed drugs on cardiovascular development. Among the compounds used in the clinic for COVD-19 treatment, we found that Remdesivir led to reduced body size and heart functionality at clinically relevant doses. Ritonavir and Baricitinib showed reduced heart functionality and Molnupiravir and Baricitinib showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than Cmax and led to a mean mortality of 20% at Cmax. Furthermore, we tested if zebrafish could be used as a model to study inflammatory response in response to spike protein treatment and found that Remdesivir, Ritonavir, Molnupiravir, Baricitinib as well as Sabizabulin counteracted the inflammatory response related gene expression upon SARS-CoV-2 spike protein treatment. Our results show that the zebrafish allows to study immune-modulating properties of COVID-19 compounds and highlights the need to rule out secondary defects of compound treatment on embryogenesis. All results are available on a user friendly web-interface https://share.streamlit.io/alernst/covasc_dataapp/main/CoVasc_DataApp.py that provides a comprehensive overview of all observed phenotypic effects and allows personalized search on specific compounds or group of compounds. Furthermore, the presented platform can be expanded for rapid detection of developmental side effects of new compounds for treatment of COVID-19 and further viral infectious diseases.Nature Publishing GroupSwiss National Science Foundation20242024-05-1020232023-10-0920232023-10-09journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/19341reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/193412026-06-12T12:43:37Z
dc.title.none.fl_str_mv Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
title Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
spellingShingle Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
Ernst, Alexander
Antiviral Agents
Embryonic Development
Animals
Female
Humans
Pregnancy
COVID-19
COVID-19 Drug Treatment
Ritonavir
SARS-CoV-2
Zebrafish
Embryo, Nonmammalian
title_short Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
title_full Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
title_fullStr Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
title_full_unstemmed Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
title_sort Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
dc.creator.none.fl_str_mv Ernst, Alexander
Piragyte, Indre
Mp, Ayisha Marwa
Le, Ngoc Dung
Grandgirard, Denis
Leib, Stephen L
Oates, Andrew
Mercader, Nadia
author Ernst, Alexander
author_facet Ernst, Alexander
Piragyte, Indre
Mp, Ayisha Marwa
Le, Ngoc Dung
Grandgirard, Denis
Leib, Stephen L
Oates, Andrew
Mercader, Nadia
author_role author
author2 Piragyte, Indre
Mp, Ayisha Marwa
Le, Ngoc Dung
Grandgirard, Denis
Leib, Stephen L
Oates, Andrew
Mercader, Nadia
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Swiss National Science Foundation
dc.subject.none.fl_str_mv Antiviral Agents
Embryonic Development
Animals
Female
Humans
Pregnancy
COVID-19
COVID-19 Drug Treatment
Ritonavir
SARS-CoV-2
Zebrafish
Embryo, Nonmammalian
topic Antiviral Agents
Embryonic Development
Animals
Female
Humans
Pregnancy
COVID-19
COVID-19 Drug Treatment
Ritonavir
SARS-CoV-2
Zebrafish
Embryo, Nonmammalian
description Drug repurposing is an important strategy in COVID-19 treatment, but many clinically approved compounds have not been extensively studied in the context of embryogenesis, thus limiting their administration during pregnancy. Here we used the zebrafish embryo model organism to test the effects of 162 marketed drugs on cardiovascular development. Among the compounds used in the clinic for COVD-19 treatment, we found that Remdesivir led to reduced body size and heart functionality at clinically relevant doses. Ritonavir and Baricitinib showed reduced heart functionality and Molnupiravir and Baricitinib showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than Cmax and led to a mean mortality of 20% at Cmax. Furthermore, we tested if zebrafish could be used as a model to study inflammatory response in response to spike protein treatment and found that Remdesivir, Ritonavir, Molnupiravir, Baricitinib as well as Sabizabulin counteracted the inflammatory response related gene expression upon SARS-CoV-2 spike protein treatment. Our results show that the zebrafish allows to study immune-modulating properties of COVID-19 compounds and highlights the need to rule out secondary defects of compound treatment on embryogenesis. All results are available on a user friendly web-interface https://share.streamlit.io/alernst/covasc_dataapp/main/CoVasc_DataApp.py that provides a comprehensive overview of all observed phenotypic effects and allows personalized search on specific compounds or group of compounds. Furthermore, the presented platform can be expanded for rapid detection of developmental side effects of new compounds for treatment of COVID-19 and further viral infectious diseases.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-10-09
2023
2023-10-09
2024
2024-05-10
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/19341
url http://hdl.handle.net/20.500.12105/19341
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410063129509888
score 15.812429

Registros relacionados