Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Canada.
Division of Geriatrics, Department of Medicine, UCLA, Los Angeles, California, United States of America.
PLoS One. 2022 Oct 26;17(10):e0271850. doi: 10.1371/journal.pone.0271850. eCollection 2022.
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.
瑞德西韦是治疗中度至重度 2 型冠状病毒（SARS-CoV-2）感染患者的主要疗法；大多数患者为老年人。瑞德西韦是一种核苷类似物，可整合到新生病毒 RNA 中，抑制 RNA 指导的 RNA 聚合酶，包括 SARS-CoV-2 的聚合酶。关于瑞德西韦对线粒体的影响知之甚少，特别是在已知线粒体功能失调的老年人中。此外，其对年龄诱导的线粒体突变和拷贝数的影响尚未得到研究。我们假设瑞德西韦会对老年啮齿动物的 mtDNA 拷贝数和缺失突变频率产生不利影响。为了验证这一假设，我们用瑞德西韦处理了 30 个月大的 F333BNF1 雄性大鼠 3 个月。为了确定瑞德西韦是否会对 mtDNA 产生不利影响，我们使用数字 PCR 测量了大鼠心脏、肾脏和骨骼肌中的 mtDNA 拷贝数和 mtDNA 缺失频率。我们发现，33 个月大的大鼠接受三个月的瑞德西韦治疗，不会影响 mtDNA 拷贝数或缺失突变频率。这些数据支持瑞德西韦在哺乳动物老年时不会损害 mtDNA 质量或数量的观点。未来的工作应集中在检查大脑和肝脏等其他组织，并将测试扩展到人类临床样本。
