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Prodrug strategies in developing antiviral nucleoside analogs
R Rama Suresh1, Tuniyazi Abuduani1, Mahesh Kasthuri1
1Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta 1760 Haygood Drive Atlanta GA 30322 USA famblar@emory.edu rschina@emory.edu.
RSC Medicinal Chemistry
|January 5, 2026
Summary
Antiviral nucleoside prodrugs enhance drug properties for better delivery. This review covers human-evaluated prodrugs, detailing approaches and benefits for treating viral infections.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Virology
Background:
- Prodrug strategies improve drug physicochemical and pharmaceutical properties.
- Prodrugs are converted to active drugs via enzymatic or chemical reactions.
- Antiviral nucleoside prodrugs are crucial in treating viral infections like SARS-CoV-2, HCV, HBV, and HIV.
Purpose of the Study:
- To review antiviral nucleoside prodrugs evaluated in humans.
- To provide an overview of different prodrug approaches.
- To discuss the in vitro and in vivo benefits of these prodrugs.
Main Methods:
- Literature review of approved, in-development, and terminated antiviral nucleoside prodrugs.
- Analysis of prodrug conversion mechanisms.
- Evaluation of pharmacokinetic and pharmacodynamic data.
Main Results:
- Successful antiviral nucleoside prodrugs improve oral bioavailability and tissue targeting.
- Various prodrug strategies have been employed for different viral targets.
- Significant clinical benefits demonstrated for approved drugs like remdesivir and tenofovir disoproxil fumarate.
Conclusions:
- Prodrug approaches are vital for effective antiviral nucleoside drug development.
- Continued research into prodrug design can overcome formulation and delivery challenges.
- Prodrugs offer a promising avenue for enhancing antiviral therapies.
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