Remdesivir triphosphate blocks DNA synthesis and increases exonucleolysis by the replicative mitochondrial DNA polymerase, Pol γ

Authors

Elena J. Ciesielska, Department of Chemistry, Auburn University at Montgomery, Montgomery, AL 36117, United States.
Shalom Kim, Department of Chemistry, Auburn University at Montgomery, Montgomery, AL 36117, United States.
Hyacintha-Ghislaine M. Bisimwa, Department of Chemistry, Auburn University at Montgomery, Montgomery, AL 36117, United States.
Cody Grier, Department of Chemistry, Auburn University at Montgomery, Montgomery, AL 36117, United States.
Md Mostafijur Rahman, Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901, United States.
Carolyn K. Young, Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901, United States.
Matthew J. Young, Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901, United States.
Marcos T. Oliveira, Departamento de Tecnologia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista "Júlio de Mesquita Filho", Jaboticabal, SP, Brazil.
Grzegorz L. Ciesielski, Department of Chemistry, Auburn University at Montgomery, Montgomery, AL 36117, United States. Electronic address: gciesiel@aum.edu.

Document Type

Article

Publication Date

11-1-2021

Subject Area

Adenosine Monophosphate (analogs & derivatives, pharmacology); Alanine (analogs & derivatives, pharmacology); COVID-19 (metabolism); Cells, Cultured; DNA Polymerase gamma (metabolism); DNA Replication (drug effects); DNA, Mitochondrial (biosynthesis); Fibroblasts (metabolism); Humans; SARS-CoV-2; COVID-19 Drug Treatment

Abstract

The COVID-19 pandemic prompted the FDA to authorize a new nucleoside analogue, remdesivir, for emergency use in affected individuals. We examined the effects of its active metabolite, remdesivir triphosphate (RTP), on the activity of the replicative mitochondrial DNA polymerase, Pol γ. We found that while RTP is not incorporated by Pol γ into a nascent DNA strand, it remains associated with the enzyme impeding its synthetic activity and stimulating exonucleolysis. In spite of that, we found no evidence for deleterious effects of remdesivir treatment on the integrity of the mitochondrial genome in human cells in culture.

Publication Title

Mitochondrion

Volume

61

First Page

147

Last Page

158

Digital Object Identifier (DOI)

10.1016/j.mito.2021.09.010

PubMed ID

34619353

E-ISSN

1872-8278

Language

eng

Citation Information

Ciesielska, Elena J.; Kim, Shalom; Bisimwa, Hyacintha-Ghislaine M.; Grier, Cody; Rahman, Md Mostafijur; Young, Carolyn K.; Young, Matthew J.; Oliveira, Marcos T.; and Ciesielski, Grzegorz L., "Remdesivir triphosphate blocks DNA synthesis and increases exonucleolysis by the replicative mitochondrial DNA polymerase, Pol γ" (2021). UNF Faculty Research and Scholarship. 3278.
https://digitalcommons.unf.edu/unf_faculty_publications/3278