{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:08:15Z","timestamp":1770818895318,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["182300410107"],"award-info":[{"award-number":["182300410107"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID\u201019) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non\u2010target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100\u2009\u03bcM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose\u2010dependent increases in mortality and malformation were observed in remdesivir\u2010treated embryos. Moreover, 10\u2013100\u2009\u03bcM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir\u2010treated group. Some of these DEGs, such as <jats:italic>manf<\/jats:italic>, <jats:italic>kif3a<\/jats:italic>, <jats:italic>hnf1ba<\/jats:italic>, <jats:italic>rgn<\/jats:italic>, <jats:italic>prkcz<\/jats:italic>, <jats:italic>egr1<\/jats:italic>, <jats:italic>fosab<\/jats:italic>, <jats:italic>nr4a1<\/jats:italic>, and <jats:italic>ptgs2b<\/jats:italic>, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos\/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir\u2010induced ecotoxicity to aquatic environments.<\/jats:p>","DOI":"10.1002\/jat.4336","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T22:24:08Z","timestamp":1652394248000},"page":"1688-1700","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The mechanism and effects of remdesivir\u2010induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations"],"prefix":"10.1002","volume":"42","author":[{"given":"Ji\u2010tong","family":"Li","sequence":"first","affiliation":[{"name":"Henan Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's 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University, Henan Children's Hospital Zhengzhou Children's Hospital  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui\u2010jing","family":"Li","sequence":"additional","affiliation":[{"name":"Henan Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010li","family":"Yang","sequence":"additional","affiliation":[{"name":"Henan Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital  Zhengzhou 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