Remdesivir does not affect mitochondrial DNA copy number or deletion mutation frequency in aged male rats: A short report

• Published in: PloS one Vol. 17; no. 10; p. e0271850
• Main Authors: Herbst, Allen, Choi, Solbie, Hoang, Austin N, Kim, Chiye, Martinez Moreno, Diana, McKenzie, Debbie, Aiken, Judd M, Wanagat, Jonathan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.10.2022; Public Library of Science (PLoS)
• Subjects: Adenosine Monophosphate - pharmacology; Alanine; Analysis; Animals; Antiviral drugs; Biology and life sciences; Child, Preschool; Copy number; Copy number variations; Coronaviruses; COVID-19; Deletion; Deoxyribonucleic acid; DNA; DNA Copy Number Variations; DNA, Mitochondrial - genetics; DNA-Directed RNA Polymerases - genetics; Gene deletion; Humans; Kidneys; Male; Males; Mammals - genetics; Medicine and Health Sciences; Mitochondria; Mitochondria - genetics; Mitochondrial DNA; Muscles; Mutation; Nucleoside analogs; Nucleosides; Older people; Rats; Ribonucleic acid; RNA; RNA, Viral; Rodents; SARS-CoV-2; Sequence Deletion; Severe acute respiratory syndrome coronavirus 2; Skeletal muscle; Viral diseases; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0271850

Remdesivir is a leading therapy in patients with moderate to severe coronavirus 2 (SARS-CoV-2) infection; the majority of whom are older individuals. Remdesivir is a nucleoside analog that incorporates into nascent viral RNA, inhibiting RNA-directed RNA polymerases, including that of SARS-CoV-2. Less is known about remdesivir's effects on mitochondria, particularly in older adults where mitochondria are known to be dysfunctional. Furthermore, its effect on age-induced mitochondrial mutations and copy number has not been previously studied. We hypothesized that remdesivir adversely affects mtDNA copy number and deletion mutation frequency in aged rodents. To test this hypothesis, 30-month-old male F333BNF1 rats were treated with remdesivir for three months. To determine if remdesivir adversely affects mtDNA, we measured copy number and mtDNA deletion frequency in rat hearts, kidneys, and skeletal muscles using digital PCR. We found no effects from three months of remdesivir treatment on mtDNA copy number or deletion mutation frequency in 33-month-old rats. These data support the notion that remdesivir does not compromise mtDNA quality or quantity at old age in mammals. Future work should focus on examining additional tissues such as brain and liver, and extend testing to human clinical samples.