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

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.