Off-Target
Adenosine Monophosphate
/ analogs & derivatives
Alanine
/ analogs & derivatives
Antiviral Agents
/ chemistry
COVID-19
/ virology
Cell Line
Epithelial Cells
/ drug effects
Humans
Inhibitory Concentration 50
Mitochondria
/ drug effects
Primary Cell Culture
SARS-CoV-2
/ drug effects
COVID-19 Drug Treatment
COVID-19
SARS-CoV-2
antiviral agents
mitochondria
mitochondrial respiration
nucleoside analogs
remdesivir
toxicity
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
20 01 2021
20 01 2021
Historique:
received:
22
10
2020
accepted:
20
11
2020
pubmed:
25
11
2020
medline:
30
1
2021
entrez:
24
11
2020
Statut:
epublish
Résumé
Remdesivir (RDV, GS-5734), the first FDA-approved antiviral for the treatment of COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. It is intracellularly metabolized into the active triphosphate form, which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases. RDV has broad-spectrum activity against members of the coronavirus family, such as SARS-CoV-2, SARS-CoV, and MERS-CoV, as well as filoviruses and paramyxoviruses. To assess the potential for off-target toxicity, RDV was evaluated in a set of cellular and biochemical assays. Cytotoxicity was evaluated in a set of relevant human cell lines and primary cells. In addition, RDV was evaluated for mitochondrial toxicity under aerobic and anaerobic metabolic conditions, and for the effects on mitochondrial DNA content, mitochondrial protein synthesis, cellular respiration, and induction of reactive oxygen species. Last, the active 5'-triphosphate metabolite of RDV, GS-443902, was evaluated for potential interaction with human DNA and RNA polymerases. Among all of the human cells tested under 5 to 14 days of continuous exposure, the 50% cytotoxic concentration (CC
Identifiants
pubmed: 33229429
pii: AAC.02237-20
doi: 10.1128/AAC.02237-20
pmc: PMC7849018
pii:
doi:
Substances chimiques
Antiviral Agents
0
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
Alanine
OF5P57N2ZX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Xu et al.
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