Prodrug strategies in developing antiviral nucleoside analogs (original) (raw)
Tuniyazi Abuduani,a Mahesh Kasthuri,a Zhe Chen,a Zahira Tber,a Mohammed Loubidi,a HongWang Zhang,a Longhu Zhou,a Shaoman Zhou,a Chenwei Li,a Amita Kumari,a Sijia Tao,a John M. Wiseman,a Selwyn J. Hurwitz,a Franck Amblard*a and Raymond F. Schinazi 
*a
* Corresponding authors
a Center 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
E-mail: famblar@emory.edu, rschina@emory.edu
Abstract
Prodrug strategies are used to enhance the physicochemical and pharmaceutical properties of drug candidates that may not be suitable for specific delivery or are limited by formulation options. A prodrug derivative is converted into its active pharmaceutical ingredient (drug) through enzymatic or chemical reactions within the body. Antiviral nucleoside prodrugs have garnered considerable interest in drug discovery, leading to the approval of key drugs such as remdesivir (SARS-CoV-2), Sovaldi (hepatitis C virus, HCV), and tenofovir disoproxil fumarate [hepatitis B virus (HBV) and human immunodeficiency viruses (HIV)]. Their success lies in improving the oral bioavailability and delivering the parent drug to the targeted tissues. This review focuses on the prodrugs of antiviral nucleosides evaluated in humans (approved, in development or terminated), providing an overview of the different approaches utilized and discussing their in vitro and in vivo benefits.
This article is Open Access
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Article information
DOI
https://doi.org/10.1039/D5MD00810G
Article type
Review Article
Submitted
11 Sep 2025
Accepted
06 Dec 2025
First published
02 Jan 2026
This article is Open Access
Download Citation
RSC Med. Chem., 2026,17, 105-131
Permissions
Prodrug strategies in developing antiviral nucleoside analogs
R. R. Suresh, T. Abuduani, M. Kasthuri, Z. Chen, Z. Tber, M. Loubidi, H. Zhang, L. Zhou, S. Zhou, C. Li, A. Kumari, S. Tao, J. M. Wiseman, S. J. Hurwitz, F. Amblard and R. F. Schinazi,RSC Med. Chem., 2026, 17, 105DOI: 10.1039/D5MD00810G
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