Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 09 2023
15 09 2023
Historique:
received:
29
05
2023
accepted:
13
09
2023
medline:
18
9
2023
pubmed:
16
9
2023
entrez:
15
9
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37714940
doi: 10.1038/s41598-023-42704-y
pii: 10.1038/s41598-023-42704-y
pmc: PMC10504289
doi:
Substances chimiques
DNA, Mitochondrial
0
remdesivir
3QKI37EEHE
Nucleosides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
15339Subventions
Organisme : NIAID NIH HHS
ID : R21 AI162775
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
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