Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation.
| Title: | Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation. |
|---|---|
| Authors: | DeFoor N; School of Neuroscience, Virginia Tech, Life Science I Room 217, 970 Washington Street SW, Blacksburg, VA, 24061, USA.; Paul S; Graduate Program in Biomedical and Veterinary Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, 24061, USA.; Li S; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.; Basso EKG; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, 24061, USA.; Stevenson V; Virginia Tech Animal Laboratory Services, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, 24061, USA.; Browning JL; School of Neuroscience, Virginia Tech, Life Science I Room 217, 970 Washington Street SW, Blacksburg, VA, 24061, USA.; Prater AK; School of Neuroscience, Virginia Tech, Life Science I Room 217, 970 Washington Street SW, Blacksburg, VA, 24061, USA.; Brindley S; School of Neuroscience, Virginia Tech, Life Science I Room 217, 970 Washington Street SW, Blacksburg, VA, 24061, USA.; Tao G; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.; Pickrell AM; School of Neuroscience, Virginia Tech, Life Science I Room 217, 970 Washington Street SW, Blacksburg, VA, 24061, USA. alicia.pickrell@vt.edu. |
| Source: | Scientific reports [Sci Rep] 2023 Sep 15; Vol. 13 (1), pp. 15339. Date of Electronic Publication: 2023 Sep 15. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Nature Publishing Group, copyright 2011- |
| MeSH Terms: | DNA, Mitochondrial*/genetics ; COVID-19*; Mitochondria/genetics ; Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Humans ; Oxidative Phosphorylation ; DNA Copy Number Variations ; Nucleosides ; COVID-19 Drug Treatment ; SARS-CoV-2 |
| Abstract: | 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.; (© 2023. Springer Nature Limited.) |
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| Grant Information: | R21 AI162775 United States AI NIAID NIH HHS |
| Substance Nomenclature: | 0 (DNA, Mitochondrial); 0 (Nucleosides); 3QKI37EEHE (remdesivir); 415SHH325A (Adenosine Monophosphate); OF5P57N2ZX (Alanine) |
| Entry Date(s): | Date Created: 20230915 Date Completed: 20230918 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10504289 |
| DOI: | 10.1038/s41598-023-42704-y |
| PMID: | 37714940 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural