School of Neuroscience
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Browsing School of Neuroscience by Subject "5 Development of treatments and therapeutic interventions"
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- Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylationDeFoor, Nicole; Paul, Swagatika; Li, Shuang; Basso, Erwin K. Gudenschwager; Stevenson, Valentina; Browning, Jack L.; Prater, Anna K.; Brindley, Samantha; Tao, Ge; Pickrell, Alicia M. (Springer, 2023-12-01)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.