Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys

Jared Pitts, J. Lizbeth Reyes Zamora, Savrina Manhas, Thomas Aeschbacher, Josolyn Chan, Vincent Cutillas, Varsha Nair, Nicholas C. Riola, Arya Vijjapurapu, Meghan S. Vermillion, Stacey Eng, Christopher Richards, Dong Han, Jason K. Perry, Subhra Chaudhuri, Szu-Wen Liu, Clarissa Martinez, Nadine Peinovich, Kai-Hui Sun, Arthur Cai, Ross Martin, Jasmine Moshiri, Charlotte Hedskog, Darius Babusis, Dustin S. Siegel, Rao Kalla, Vasanthi Avadhanula, Pedro A. Piedra, Kim Stobbelaar, Peter L. Delputte, Caleb Marceau, Roberto Mateo, Evguenia Maiorova, Hongmei Mo, Raju Subramanian, Richard L. Mackman, Tomas Cihlar, Simon P. Fletcher and John P. Bilello ()
Additional contact information
Jared Pitts: Inc.
J. Lizbeth Reyes Zamora: Inc.
Savrina Manhas: Inc.
Thomas Aeschbacher: Inc.
Josolyn Chan: Inc.
Vincent Cutillas: Inc.
Varsha Nair: Inc.
Nicholas C. Riola: Inc.
Arya Vijjapurapu: Inc.
Meghan S. Vermillion: Lovelace Biomedical Research Institute
Stacey Eng: Inc.
Christopher Richards: Inc.
Dong Han: Inc.
Jason K. Perry: Inc.
Subhra Chaudhuri: Inc.
Szu-Wen Liu: Inc.
Clarissa Martinez: Inc.
Nadine Peinovich: Inc.
Kai-Hui Sun: Inc.
Arthur Cai: Inc.
Ross Martin: Inc.
Jasmine Moshiri: Inc.
Charlotte Hedskog: Inc.
Darius Babusis: Inc.
Dustin S. Siegel: Inc.
Rao Kalla: Inc.
Vasanthi Avadhanula: Baylor College of Medicine
Pedro A. Piedra: Baylor College of Medicine
Kim Stobbelaar: University of Antwerp
Peter L. Delputte: University of Antwerp
Caleb Marceau: Inc.
Roberto Mateo: Inc.
Evguenia Maiorova: Inc.
Hongmei Mo: Inc.
Raju Subramanian: Inc.
Richard L. Mackman: Inc.
Tomas Cihlar: Inc.
Simon P. Fletcher: Inc.
John P. Bilello: Inc.

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC50: 0.20–0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identify a single amino acid substitution, I777L, in the L polymerase with reduced susceptibility (3.3-3.8-fold) to ODV and GS-441524, indicating a high barrier for resistance development. In an African green monkey RSV infection model, once-daily oral ODV doses of 30 or 90 mg/kg initiated ~24 hours post-infection significantly reduces log10 viral RNA copies/mL × day area under the curve by 69–92% in the upper and lower respiratory tracts. Together, these preclinical data support the clinical evaluation of ODV for the treatment of RSV infection.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61595-3 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:16:y:2025:i:1:d:10.1038_s41467-025-61595-3

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

DOI: 10.1038/s41467-025-61595-3

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 ().