Addressing the selectivity and toxicity of antiviral nucleosides.
Addressing the selectivity and toxicity of antiviral nucleosides.
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DOI：
10.1177/2040206618758524
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发表时间：
2018-01
影响因子：
--
通讯作者：
Feng JY
中科院分区：
文献类型：
--
作者：
Feng JY
核苷和核苷酸类似物在抗病毒治疗中发挥了重要作用，并因其令人印象深刻的效力和高耐药性屏障而受到重视。它们已被批准用于治疗单纯疱疹病毒-1、HIV、HBV、HCV和流感，并且正在开发用于治疗RSV、埃博拉病毒、冠状病毒MERS和其他新兴病毒的新药。然而，由于毒性，这类化合物在临床试验中也经历了高损耗率。在这篇综述中，我们讨论了不同的生物化学和细胞为基础的测定的效用，并提供了进入动物毒性研究之前评估毒性倾向的建议。
Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.