Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation.

Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation.

Publication date: Sep 15, 2023

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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Concepts Keywords
Antiviral Alterations
Fda Analogues
Increase32 Causing
Insightful Copy
Ribonucleoside Covid


Type Source Name
pathway KEGG Oxidative phosphorylation
disease MESH causes
disease MESH COVID-19
drug DRUGBANK Adenosine
disease MESH mitochondrial disease
drug DRUGBANK Coenzyme M
drug DRUGBANK Troleandomycin
disease IDO host
drug DRUGBANK L-Alanine
drug DRUGBANK Angiotensin II
disease MESH Middle East respiratory syndrome
drug DRUGBANK Succinic acid
drug DRUGBANK Iron
disease VO IroN
drug DRUGBANK Zidovudine
disease VO USA
disease MESH infections
drug DRUGBANK Tocilizumab
drug DRUGBANK Baricitinib
drug DRUGBANK Trestolone
disease MESH Emergency
disease IDO replication
disease IDO cell
disease MESH defects
drug DRUGBANK Deoxythymidine
disease MESH AIDS
disease MESH myopathies
disease VO dose
disease VO efficiency
disease VO viability
disease IDO blood
disease MESH incidental finding
disease MESH point mutation
disease MESH hepatitis
disease VO Viruses
disease MESH hypotension
disease MESH bradycardia
disease MESH viral infections
disease MESH chronic hepatitis
disease MESH hepatic failure
disease MESH lactic acidosis
disease MESH pancreatitis
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Methylergometrine
drug DRUGBANK Amino acids
drug DRUGBANK L-Glutamine
disease VO Mycoplasma
drug DRUGBANK Dimethyl sulfoxide
disease IDO pathogen
disease IDO facility
drug DRUGBANK Water
drug DRUGBANK Sulodexide
disease VO intraperitoneal injection
drug DRUGBANK Ketamine
drug DRUGBANK Xylazine
drug DRUGBANK Nitrogen
drug DRUGBANK Formaldehyde
disease IDO assay
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Edetic Acid
drug DRUGBANK Phenol
drug DRUGBANK Isopropyl Alcohol
drug DRUGBANK Ethanol
drug DRUGBANK Thiocolchicoside
drug DRUGBANK Timonacic
disease VO Tat
disease VO TTC
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK 5-amino-1 3 4-thiadiazole-2-thiol
drug DRUGBANK 7-Methyl-Gpppa
drug DRUGBANK Hyaluronic acid
drug DRUGBANK Monopotassium phosphate
drug DRUGBANK Gold
drug DRUGBANK L-Citrulline
drug DRUGBANK Heparin
disease MESH death
disease VO frequency
disease VO ANOVA
disease VO organization
disease VO report
disease MESH Drug Interaction
disease MESH syndrome
disease IDO infectivity
disease MESH lymphadenopathy
disease MESH AIDS related complex
drug DRUGBANK Guanosine
disease MESH oxidative stress
drug DRUGBANK Iodide
disease MESH severe acute respiratory syndrome
disease MESH carcinogenesis
disease MESH Mitochondrial myopathy
disease MESH Cardiomyopathy
disease MESH HIV infection
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH Herpes simplex
disease MESH mutation frequency
drug DRUGBANK Tropicamide
disease VO time

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