Phosphoramidate Prodrugs Continue to Deliver: The Journey of Remdesivir (GS-5734) from the Liver to Peripheral Blood Mononuclear Cells

Abstract

Remdesivir (GS-5734) is a monophenol, 2-ethylbutylalanine phosphoramidate prodrug of GS-441524 that is FDA-approved for the treatment of patients hospitalized for COVID-19. Despite showing strong, broad-spectrum antiviral activity in preclinical models, the clinical efficacy of remdesivir is mixed. This work highlights the pharmacodynamic discordance of remdesivir between humans and non-human primates, thereby demonstrating that non-human primate disease models overestimate the therapeutic efficacy of phosphoramidate prodrugs.