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抗性屏障而受到重视。它们已被批准用于治疗单纯疱疹病毒-1,HIV,HBV,HCV,和流感,正在开发用于治疗RSV的新药,埃博拉病毒,冠状病毒MERS,和其他新兴病毒。然而,由于毒性,这类化合物在临床试验中也经历了很高的损耗率。在这次审查中,我们讨论了不同的生化和基于细胞的检测方法的实用性,并在进入动物毒性研究之前为评估毒性作用提供了建议.
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.