Comparison of anti-SARS-CoV-2 activity and intracellular metabolism of remdesivir and its parent nucleoside

  • Curr Res Pharmacol Drug Discov. 2021:2:100045. doi: 10.1016/j.crphar.2021.100045.
Sijia Tao  1 ,  Keivan Zandi  1 ,  Leda Bassit  1 ,  Yee Tsuey Ong  1 ,  Kiran Verma  1 ,  Peng Liu  1 ,  Jessica A Downs-Bowen  1 ,  Tamara McBrayer  1 ,  Julia C LeCher  1 ,  James J Kohler  1 ,  Philip R Tedbury  1 ,  Baek Kim  1 ,  Franck Amblard  1 ,  Stefan G Sarafianos  1 ,  Raymond F Schinazi  1
Affiliations
  • 1. Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
PMID: 34870151 DOI: 10.1016/j.crphar.2021.100045
Abstract

Remdesivir, a monophosphate prodrug of nucleoside analog GS-441524, is widely used for the treatment of moderate to severe COVID-19. It has been suggested to use GS-441524 instead of remdesivir in the clinic and in new inhalation formulations. Thus, we compared the anti-SARS-CoV-2 activity of remdesivir and GS-441524 in Vero E6, Vero CCL-81, Calu-3, Caco-2 ​cells, and anti-HCoV-OC43 activity in Huh-7 ​cells. We also compared the cellular pharmacology of these two compounds in Vero E6, Vero CCL-81, Calu-3, Caco-2, Huh-7, 293T, BHK-21, 3T3 and human airway epithelial (HAE) cells. Overall, remdesivir exhibited greater potency and superior intracellular metabolism than GS-441524 except in Vero E6 and Vero CCL-81 ​cells.

Keywords
ACE2, angiotensin-converting enzyme 2; Anti-SARS-CoV-2; Antiviral agents; CES1, carboxylesterase 1; COVID-19; COVID-19, coronavirus disease 2019; CatA, cathepsin A; Coronavirus; DP, diphosphate; GS-441524; HAE, human airway epithelial; HCoV-OC43; HINT1, histidine triad nucleotide-binding protein 1; MP, monophosphate; NTP, nucleoside triphosphate; Pharmacology; Remdesivir; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TP, triphosphate; WHO, World Health Organization; icSARS-CoV-2-mNG, SARS-CoV-2 infectious clone virus containing mNeonGreen reporter.
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