Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation

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dc.contributor.authorDeFoor, Nicoleen
dc.contributor.authorPaul, Swagatikaen
dc.contributor.authorLi, Shuangen
dc.contributor.authorBasso, Erwin K. Gudenschwageren
dc.contributor.authorStevenson, Valentinaen
dc.contributor.authorBrowning, Jack L.en
dc.contributor.authorPrater, Anna K.en
dc.contributor.authorBrindley, Samanthaen
dc.contributor.authorTao, Geen
dc.contributor.authorPickrell, Alicia M.en
dc.date.accessioned2023-10-30T19:21:01Zen
dc.date.available2023-10-30T19:21:01Zen
dc.date.issued2023-12-01en
dc.date.updated2023-10-30T19:15:55Zen
dc.description.abstractSARS-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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier15339 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-023-42704-yen
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidPickrell, Alicia [0000-0002-8470-6056]en
dc.identifier.other10.1038/s41598-023-42704-y (PII)en
dc.identifier.pmid37714940en
dc.identifier.urihttp://hdl.handle.net/10919/116575en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherSpringeren
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/37714940en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subject3101 Biochemistry and Cell Biologyen
dc.subject31 Biological Sciencesen
dc.subjectGeneticsen
dc.subject5 Development of treatments and therapeutic interventionsen
dc.subject5.1 Pharmaceuticalsen
dc.subject.meshMitochondriaen
dc.subject.meshHumansen
dc.subject.meshNucleosidesen
dc.subject.meshDNA, Mitochondrialen
dc.subject.meshOxidative Phosphorylationen
dc.subject.meshDNA Copy Number Variationsen
dc.subject.meshCOVID-19en
dc.subject.meshSARS-CoV-2en
dc.subject.meshCOVID-19 Drug Treatmenten
dc.titleRemdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylationen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2023-09-13en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen

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