Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation.
Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation.
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DOI：
10.1038/s41598-023-42704-y
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发表时间：
2023-09-15
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
SARS-CoV-2导致严重的呼吸道疾病COVID-19。Remdesivir（RDV）是FDA批准的第一种快速治疗COVID-19的药物。RDV作为一种抗病毒核糖核苷（腺苷）类似物，一旦在细胞内积累就变得活跃。然后它扩散到宿主细胞中并终止病毒RNA转录。以前的研究表明，某些核苷类似物无意中抑制线粒体RNA或DNA聚合酶或导致线粒体DNA（mtDNA）突变。这些关于核糖核苷类似物的线粒体毒性的过去的发现促使我们研究RDV可能对线粒体功能有什么影响。使用体外和体内啮齿动物模型，我们观察到在处理后，Mv 1 Lu细胞（增加35.26% ± 11.33%）和肝脏（增加100.27% ± 32.73%）中mtDNA拷贝数增加。然而，这些增加仅导致线粒体功能的轻度变化。令人惊讶的是，骨骼肌和心脏对RDV治疗具有极强的抗性，这些组织优先受到其他核苷类似物的影响。虽然我们的数据表明，RDV不会极大地影响线粒体功能，但这些数据对于治疗患有线粒体疾病的个体的RDV是有见地的。
SARS-CoV-2 causes the severe respiratory disease COVID-19. Remdesivir (RDV) was the first fast-tracked FDA approved treatment drug for COVID-19. RDV acts as an antiviral ribonucleoside (adenosine) analogue that becomes active once it accumulates intracellularly. It then diffuses into the host cell and terminates viral RNA transcription. Previous studies have shown that certain nucleoside analogues unintentionally inhibit mitochondrial RNA or DNA polymerases or cause mutational changes to mitochondrial DNA (mtDNA). These past findings on the mitochondrial toxicity of ribonucleoside analogues motivated us to investigate what effects RDV may have on mitochondrial function. Using in vitro and in vivo rodent models treated with RDV, we observed increases in mtDNA copy number in Mv1Lu cells (35.26% increase ± 11.33%) and liver (100.27% increase ± 32.73%) upon treatment. However, these increases only resulted in mild changes to mitochondrial function. Surprisingly, skeletal muscle and heart were extremely resistant to RDV treatment, tissues that have preferentially been affected by other nucleoside analogues. Although our data suggest that RDV does not greatly impact mitochondrial function, these data are insightful for the treatment of RDV for individuals with mitochondrial disease.
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影响因子：
4.6
作者：
Heallen, Todd;Morikawa, Yuka;Martin, James F.
通讯作者：
Martin, James F.
DOI：
10.1016/j.future.2018.04.037
发表时间：
2019-05
期刊：
Future generations computer systems : FGCS
影响因子：
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作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
3.8
作者：
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通讯作者：
Wallace KB
影响因子：
4.5
作者：
Humeniuk R;Mathias A;Kirby BJ;Lutz JD;Cao H;Osinusi A;Babusis D;Porter D;Wei X;Ling J;Reddy YS;German P
通讯作者：
German P