Novel immunomodulatory properties of adenosine analogs promote their antiviral activity against SARS-CoV-2
Document Type
Article
Publication Date
7-15-2024
Publication Title
EMBO Reports
Abstract
The COVID-19 pandemic reminded us of the urgent need for new antivirals to control emerging infectious diseases and potential future pandemics. Immunotherapy has revolutionized oncology and could complement the use of antivirals, but its application to infectious diseases remains largely unexplored. Nucleoside analogs are a class of agents widely used as antiviral and anti-neoplastic drugs. Their antiviral activity is generally based on interference with viral nucleic acid replication or transcription. Based on our previous work and computer modeling, we hypothesize that antiviral adenosine analogs, like remdesivir, have previously unrecognized immunomodulatory properties which contribute to their therapeutic activity. In the case of remdesivir, we here show that these properties are due to its metabolite, GS-441524, acting as an Adenosine A2A Receptor antagonist. Our findings support a new rationale for the design of next-generation antiviral agents with dual - immunomodulatory and intrinsic - antiviral properties. These compounds could represent game-changing therapies to control emerging viral diseases and future pandemics.
PubMed ID
39009832
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Monticone, Giulia; Huang, Zhi; Hewins, Peter; Cook, Thomasina; Mirzalieva, Oygul; King, Brionna; Larter, Kristina; Miller-Ensminger, Taylor; Sanchez-Pino, Maria D.; Foster, Timothy P.; Nichols, Olga V.; Ramsay, Alistair J.; Majumder, Samarpan; Wyczechowska, Dorota; Tauzier, Darlene; Gravois, Elizabeth; Crabtree, Judy S.; Garai, Jone; Li, Li; Zabaleta, Jovanny jzabal@lsuhsc.edu; Barbier, Mallory T.; Del Valle, Luis; Jurado, Kellie A.; and Miele, Lucio, "Novel immunomodulatory properties of adenosine analogs promote their antiviral activity against SARS-CoV-2" (2024). School of Medicine Faculty Publications. 2846.
https://digitalscholar.lsuhsc.edu/som_facpubs/2846
10.1038/s44319-024-00189-4