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

Robert M. Cox, Josef D. Wolf, Carolin M. Lieber, Julien Sourimant, Michelle J. Lin, Darius Babusis, Venice DuPont, Julie Chan, Kim T. Barrett, Diane Lye, Rao Kalla, Kwon Chun, Richard L. Mackman, Chengjin Ye, Tomas Cihlar, Luis Martinez-Sobrido, Alexander L. Greninger, John P. Bilello and Richard K. Plemper ()
Additional contact information
Robert M. Cox: Georgia State University
Josef D. Wolf: Georgia State University
Carolin M. Lieber: Georgia State University
Julien Sourimant: Georgia State University
Michelle J. Lin: University of Washington
Darius Babusis: Gilead Sciences Inc
Venice DuPont: Gilead Sciences Inc
Julie Chan: Gilead Sciences Inc
Kim T. Barrett: Gilead Sciences Inc
Diane Lye: Gilead Sciences Inc
Rao Kalla: Gilead Sciences Inc
Kwon Chun: Gilead Sciences Inc
Richard L. Mackman: Gilead Sciences Inc
Chengjin Ye: Texas Biomedical Research Institute
Tomas Cihlar: Gilead Sciences Inc
Luis Martinez-Sobrido: Texas Biomedical Research Institute
Alexander L. Greninger: University of Washington
John P. Bilello: Gilead Sciences Inc
Richard K. Plemper: Georgia State University

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26760-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26760-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26760-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().