2026-07-22T08:14:26Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/193412024-09-27T08:06:03Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Ernst, Alexander
author
Piragyte, Indre
author
Mp, Ayisha Marwa
author
Le, Ngoc Dung
author
Grandgirard, Denis
author
Leib, Stephen L
author
Oates, Andrew
author
Mercader, Nadia
funder
Swiss National Science Foundation
2024-05-10T07:36:19Z
2024-05-10T07:36:19Z
2023-10-09
Sci Rep. 2023 Oct 9;13(1):17037.
10.1038/s41598-023-43911-3
2045-2322
Scientific reports
37813860
http://hdl.handle.net/20.500.12105/19341
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.
eng
Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.
journal article
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https://repisalud.isciii.es/bitstreams/8bbb0966-2227-4f0e-8733-ae53866b4743/download
File
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application/pdf
Identification of side effects of COVID_19 drug_Sci Rep_2023.pdf
URL
https://repisalud.isciii.es/bitstreams/c1e50a68-f625-43b1-af10-02f107e5994c/download
File
MD5
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text/plain
Identification of side effects of COVID_19 drug_Sci Rep_2023.pdf.txt