使用集成斑马鱼查平台识别COVID-19候选药物对胚胎发生的副作用
Alexander Ernst1, Indre Piragyte1,2, Ayisha Marwa Mp1,2
1Institute of Anatomy, University of Bern, Bern, Switzerland.
Scientific reports
|October 9, 2023
概括
斑马鱼胚胎揭示了Remdesivir和Molnupiravir等COVID-19药物对心血管功能和胚胎活动的发育缺陷. 然而,这些药物也抵消了由SARS-CoV-2尖端蛋白诱导的炎症基因表达.
科学领域:
- 发育生物学是发展生物学.
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
背景情况:
- 用于COVID-19治疗的药物重新定位至关重要,但批准药物的潜在胚胎发生效应通常未经检查,限制了怀孕期间的使用.
- 了解COVID-19疗法对胚胎发育的影响对于安全的临床应用至关重要.
研究的目的:
- 评估包括COVID-19治疗在内的162种已上市药物的对斑马鱼胚胎心血管发育的影响.
- 评估斑马鱼胚胎的实用性,作为研究COVID-19化合物的免疫调节特性和发育副作用的模型.
主要方法:
- 选了162种在市场上销售的药物,以检测对斑马鱼胚胎心血管发育和整体活性的影响.
- 研究了在斑马鱼中针对SARS-CoV-2尖端蛋白诱导基因表达的选定COVID-19药物的抗炎作用.
- 利用网页界面进行数据可视化和观察到的表型效应的分析.
主要成果:
- 雷梅西维尔,里托纳维尔,莫尔努皮拉维尔和巴里西提尼布在临床相关剂量时表现出不同程度的心血管功能障碍和/或胚胎活性降低.
- 萨比扎布林在接近其最大观测度 (Cmax) 的度下显示出高毒性和显著的死亡率.
- 雷梅西维尔,里托纳维尔,莫尔努皮拉维尔,巴里西丁尼和萨比扎布林有效抵消了由SARS-CoV-2尖端蛋白引发的炎症基因表达.
结论:
- 斑马鱼胚胎是评估COVID-19药物的发育毒性和免疫调节潜力的宝贵模型.
- 这项研究强调了评估二次胚胎发生缺陷对于被考虑用于COVID-19治疗的药物的必要性,特别是在孕妇中.
- 开发了一个用户友好的网络平台,共享药物效应的全面数据,促进进一步的研究和药物查.
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