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Open Access CC BY-NC-ND V4.0
Journal article
Metabolism and Excretion of Synthetic Extended Viperin Pathway Deoxydidehydronucleosides in the Sprague-Dawley Rat
Journal of proteome research
2026
PMID: 42128411
Abstract
Broad-spectrum viral biomarkers offer a promising approach to distinguishing viral from bacterial infections, thereby reducing inappropriate antibiotic use and improving diagnostic response during emerging infectious disease outbreaks. Among these, the deoxydidehydronucleoside (ddhN) class of nucleoside derivatives has emerged as a potential tool for early detection of viral infections in settings where pathogen-specific diagnostics are unavailable. To assess the clinical utility of these compounds, we investigated the metabolism and excretion rates of four principal ddhN metabolites, 3'-deoxy-3',4'-didehydrocytidine (ddhC), 3'-deoxy-3',4'-didehydrocytidine-5'-carboxylate (ddhC-5'CA), 3'-deoxy-3',4'-didehydrouridine (ddhU), and 3'-deoxy-3',4'-didehydrocytidine-5'-homocysteine (ddhC-5'Hcy), in the Sprague-Dawley rat model following a single intravenous dose. Time-resolved biological sampling was used to characterize urinary excretion and downstream biotransformation. All four metabolites exhibited rapid urinary clearance, ranging from approximately 3 to 8 h, consistent with a transient acute-phase profile. Notably, ddhC-5'Hcy underwent extensive biotransformation, with key metabolites produced via functionalization and conjugation identified following integration of nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) analyses. No adverse clinical signs were observed in any treatment group at any time point. These findings support further research into the ddhN series as markers of active viral infection for clinical application, particularly in critical care environments, where timely differentiation of infectious etiology is essential.
Details
- Title
- Metabolism and Excretion of Synthetic Extended Viperin Pathway Deoxydidehydronucleosides in the Sprague-Dawley Rat
- Authors/Creators
- Samuele Sala - Murdoch UniversityPhilipp Nitschke - Murdoch UniversityAndres M Castillo - Murdoch UniversityAndres Bernal - Murdoch UniversityReika Masuda - Murdoch UniversityJames M Wood - Victoria University of WellingtonJoshua N Buckler - Victoria University of WellingtonTyler L Grove - Albert Einstein College of MedicineSteven C Almo - Albert Einstein College of MedicineLawrence D Harris - University of AucklandElaine Holmes - Murdoch University, Centre for Computational and Systems MedicineJulien Wist - Murdoch UniversityIan D Wilson - Imperial College LondonJeremy K Nicholson - Imperial College London
- Publication Details
- Journal of proteome research
- Publisher
- American Chemical Society
- Number of pages
- 10
- Identifiers
- 991005883919807891
- Copyright
- © 2026 The Authors
- Murdoch Affiliation
- Centre for Computational and Systems Medicine
- Language
- English
- Resource Type
- Journal article
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