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

Author: ErnstAlexander, GrandgirardDenis, LeNgoc Dung, LeibStephen L, MercaderNadia, MpAyisha Marwa, OatesAndrew, PiragyteIndre

ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Overview

This study investigated the effects of 162 marketed drugs on cardiovascular development in zebrafish embryos. It was found that Remdesivir reduced body size and heart functionality at clinically relevant doses, while Ritonavir and Baricitinib showed reduced heart functionality. Molnupiravir and Baricitinib also showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than the maximum concentration reached in the blood after administration, and led to a mean mortality of 20% at that maximum concentration. The study also found that zebrafish can be used as a model to study the inflammatory response to SARS-CoV-2 spike protein treatment, and that Remdesivir, Ritonavir, Molnupiravir, Baricitinib, and Sabizabulin counteracted the inflammatory response related gene expression upon spike protein treatment. These findings highlight the need to rule out potential side effects of drugs on embryogenesis, and demonstrate the usefulness of zebrafish in studying the immune-modulating properties of COVID-19 compounds.
Paper Details　
Original Abstract of the Article :
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 ...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562458/

データ提供：米国国立医学図書館（NLM）

Zebrafish: Tiny Swimmers, Big Insights into Drug Safety

The development of new [drug candidates] is a complex and time-consuming process. One of the crucial steps is evaluating the safety of these drugs, especially during [embryogenesis]. This study utilizes the [zebrafish embryo model] to assess the potential side effects of [162 marketed drugs] on [cardiovascular development]. Zebrafish embryos have emerged as a powerful tool for studying drug safety due to their rapid development and genetic similarities to humans.

The researchers identified several drugs, including [Remdesivir, Ritonavir, Baricitinib, Molnupiravir, and Sabizabulin], that exhibited negative effects on zebrafish embryos, highlighting the importance of further investigation into their potential impact on human development.

Zebrafish: A Window into Drug Safety

This study demonstrates the value of using zebrafish embryos as a model organism to screen drug candidates for potential developmental side effects. The findings underscore the importance of conducting thorough safety assessments before administering drugs during pregnancy to minimize potential risks to the developing fetus.

Prioritizing Safe Drug Development

This research emphasizes the need for rigorous drug safety testing, particularly during pregnancy. By employing model organisms like zebrafish, researchers can gain valuable insights into the potential developmental effects of drugs, contributing to the development of safer and more effective medications.

Dr.Camel's Conclusion

Just as a camel relies on its keen senses to navigate the desert, researchers are utilizing zebrafish as a sensory tool to detect potential dangers in the vast landscape of drug development. By understanding the potential impact of drugs on developing embryos, we can ensure a safer journey for both mother and child.

Date :
  1. Date Completed 2023-10-11
  2. Date Revised 2023-11-21
Further Info :

Pubmed ID

37813860

DOI: Digital Object Identifier

PMC10562458

SNS
PICO Info
in preparation
Languages

English

Positive IndicatorAn AI analysis index that serves as a benchmark for how positive the results of the study are. Note that it is a benchmark and requires careful interpretation and consideration of different perspectives.

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