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

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 remdes...

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Published in:Current research in pharmacology and drug discovery 2021-01, Vol.2, p.100045-100045, Article 100045
Main Authors: Tao, Sijia, Zandi, Keivan, Bassit, Leda, Ong, Yee Tsuey, Verma, Kiran, Liu, Peng, Downs-Bowen, Jessica A., McBrayer, Tamara, LeCher, Julia C., Kohler, James J., Tedbury, Philip R., Kim, Baek, Amblard, Franck, Sarafianos, Stefan G., Schinazi, Raymond F.
Format: Article
Language:English
Subjects:
Anti-SARS-CoV-2
Antiviral agents
Coronavirus
COVID-19
COVID-19 therapy
GS-441524
HCoV-OC43
Pharmacology
Remdesivir
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Summary: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. [Display omitted] •Anti-SARS-CoV-2 potency of remdesivir is similar to GS-441524 in Vero cells, but higher in Calu-3 and Caco-2 ​cells.•Anti-HCoV-OC43 activity of remdesivir is higher than GS-441524 in Huh-7 ​cells.•Cellular level of GS-443902 positively correlates with the anti-coronavirus activity in Calu-3, Caco-2 and Huh-7 ​cells.•Remdesivir exhibits superior cellular metabolism than GS-441524 in 293T, BHK-21, 3T3 and human airway epithelial cells.
ISSN:2590-2571
2590-2571
DOI:10.1016/j.crphar.2021.100045