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Updated: Jun 14, 2026

Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening
Alexander Ernst1, Indre Piragyte1,2, Ayisha Marwa Mp1,2
1Institute of Anatomy, University of Bern, Bern, Switzerland.
Abstract:
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.
Insights
Zebrafish embryos revealed developmental defects in cardiovascular function and embryo activity from COVID-19 drugs like Remdesivir and Molnupiravir. However, these drugs also counteracted inflammatory gene expression induced by the SARS-CoV-2 spike protein.
Area of Science:
- Developmental biology
- Pharmacology
- Toxicology
Background:
- Drug repurposing for COVID-19 treatment is crucial, but potential embryogenesis effects of approved drugs are often unexamined, limiting use during pregnancy.
- Understanding the impact of COVID-19 therapeutics on embryonic development is essential for safe clinical application.
Purpose of the Study:
- To evaluate the effects of 162 marketed drugs, including COVID-19 treatments, on zebrafish embryo cardiovascular development.
- To assess the utility of zebrafish embryos as a model for studying the immune-modulating properties and developmental side effects of COVID-19 compounds.
Main Methods:
- Screened 162 marketed drugs for effects on zebrafish embryo cardiovascular development and overall activity.
- Investigated the anti-inflammatory effects of selected COVID-19 drugs against SARS-CoV-2 spike protein-induced gene expression in zebrafish.
- Utilized a web interface for data visualization and analysis of observed phenotypic effects.
Main Results:
- Remdesivir, Ritonavir, Molnupiravir, and Baricitinib exhibited varying degrees of cardiovascular dysfunction and/or reduced embryo activity at clinically relevant doses.
- Sabizabulin demonstrated high toxicity and significant mortality at concentrations near its maximum observed concentration (Cmax).
- Remdesivir, Ritonavir, Molnupiravir, Baricitinib, and Sabizabulin effectively counteracted inflammatory gene expression triggered by the SARS-CoV-2 spike protein.
Conclusions:
- Zebrafish embryos serve as a valuable model for assessing both the developmental toxicity and immunomodulatory potential of COVID-19 drugs.
- The study highlights the necessity of evaluating secondary embryogenesis defects for drugs considered for COVID-19 treatment, especially in pregnant individuals.
- A user-friendly web platform was developed to share comprehensive data on drug effects, facilitating further research and drug screening.
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