Remdesivir does not affect mitochondrial DNA copy number or deletion mutation frequency in aged male rats: A short report.
Remdesivir does not affect mitochondrial DNA copy number or deletion mutation frequency in aged male rats: A short report.
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DOI：
10.1371/journal.pone.0271850
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
瑞德西韦是中至重度冠状病毒2型（SARS-CoV-2）感染患者的主要治疗药物；其中大多数是老年人。Remdesivir是一种核苷类似物，可融入新生病毒RNA，抑制RNA导向的RNA聚合酶，包括SARS-CoV-2的RNA聚合酶。关于瑞德西韦对线粒体的影响，特别是对线粒体功能失调的老年人的影响，我们所知甚少。此外，其对年龄诱导的线粒体突变和拷贝数的影响尚未被研究。我们假设瑞德西韦对老年啮齿动物的mtDNA拷贝数和缺失突变频率有不利影响。为了验证这一假设，30个月大的雄性F333BNF1大鼠用瑞德西韦治疗了3个月。为了确定瑞德西韦是否对mtDNA有不良影响，我们使用数字PCR测量了大鼠心脏、肾脏和骨骼肌的mtDNA拷贝数和缺失频率。我们发现3个月的瑞德西韦治疗对33月龄大鼠mtDNA拷贝数或缺失突变频率没有影响。这些数据支持瑞德西韦不会影响哺乳动物老年mtDNA质量或数量的观点。未来的工作应侧重于检查其他组织，如大脑和肝脏，并将测试扩展到人类临床样本。
Remdesivir is a leading therapy in patients with moderate to severe coronavirus 2 (SARS-CoV-2) infection; the majority of whom are older individuals. Remdesivir is a nucleoside analog that incorporates into nascent viral RNA, inhibiting RNA-directed RNA polymerases, including that of SARS-CoV-2. Less is known about remdesivir’s effects on mitochondria, particularly in older adults where mitochondria are known to be dysfunctional. Furthermore, its effect on age-induced mitochondrial mutations and copy number has not been previously studied. We hypothesized that remdesivir adversely affects mtDNA copy number and deletion mutation frequency in aged rodents. To test this hypothesis, 30-month-old male F333BNF1 rats were treated with remdesivir for three months. To determine if remdesivir adversely affects mtDNA, we measured copy number and mtDNA deletion frequency in rat hearts, kidneys, and skeletal muscles using digital PCR. We found no effects from three months of remdesivir treatment on mtDNA copy number or deletion mutation frequency in 33-month-old rats. These data support the notion that remdesivir does not compromise mtDNA quality or quantity at old age in mammals. Future work should focus on examining additional tissues such as brain and liver, and extend testing to human clinical samples.
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