Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets.

Cox, Robert M, Josef D Wolf, Carolin M Lieber, Julien Sourimant, Michelle J Lin, Darius Babusis, Venice DuPont, et al. 2021. “Oral Prodrug of Remdesivir Parent GS-441524 Is Efficacious Against SARS-CoV-2 in Ferrets.”. Nature Communications 12 (1): 6415.

Abstract

Remdesivir is an antiviral approved for COVID-19 treatment, but its wider use is limited by intravenous delivery. An orally bioavailable remdesivir analog may boost therapeutic benefit by facilitating early administration to non-hospitalized patients. This study characterizes the anti-SARS-CoV-2 efficacy of GS-621763, an oral prodrug of remdesivir parent nucleoside GS-441524. Both GS-621763 and GS-441524 inhibit SARS-CoV-2, including variants of concern (VOC) in cell culture and human airway epithelium organoids. Oral GS-621763 is efficiently converted to plasma metabolite GS-441524, and in lungs to the triphosphate metabolite identical to that generated by remdesivir, demonstrating a consistent mechanism of activity. Twice-daily oral administration of 10 mg/kg GS-621763 reduces SARS-CoV-2 burden to near-undetectable levels in ferrets. When dosed therapeutically against VOC P.1 gamma γ, oral GS-621763 blocks virus replication and prevents transmission to untreated contact animals. These results demonstrate therapeutic efficacy of a much-needed orally bioavailable analog of remdesivir in a relevant animal model of SARS-CoV-2 infection.

Last updated on 12/14/2023
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