Antiviral Activity of the Acyclic Nucleoside Phosphonate Prodrug LAVR-289 against Poxviruses and African Swine Fever Virus
Poxviruses are double-stranded DNA viruses including relevant zoonotic pathogens with high morbidity and potential biological warfare threats. Although African swine fever virus belongs to the <i>Asfarviridae</i> family and is not strictly classified as a <i>Poxviridae</i> member, both fall within the same class of <i>Pokkesviricetes</i> that replicate in the cytoplasm. Among compounds targeting these viruses, acyclic nucleoside phosphonate (ANP) prodrugs are promising inhibitors of viral DNA polymerases. However, some limitations related to their toxicity and the rapid emergence of resistance highlight the need for new antiviral molecules. In this study, we tested a new ANP called LAVR-289. This product effectively inhibits viral replication by targeting a specific domain in the poxvirus DNA polymerase. Using monkeypox virus models, the subcutaneous or oral administration of LAVR-289 demonstrated protective efficacy in infected animals without toxicity. Its <i>in vivo</i> half-life, long on-the-shelf stability and broad-spectrum efficacy make LAVR-289 a promising candidate for further development and stockpiling as a medical countermeasure against dsDNA virus outbreaks. LAVR-289 can be positioned in the context of recurrent viral epidemics, bioterrorism risk, and the emergence of resistant strains in the population.
Authors
- Frédéric Iseni (ORCID: https://orcid.org/0000-0003-3909-9688)
- Mathilde Keck (ORCID: https://orcid.org/0000-0003-4717-3446)
- Joseph W. Golden (ORCID: https://orcid.org/0000-0002-9709-313X)
- Joshua D. Shamblin (ORCID: https://orcid.org/0000-0003-0135-3812)
- Peggy Barbe
- Daniel Gillet (ORCID: https://orcid.org/0000-0003-0477-3599)
- Sandrine Kappler‐Gratias
- Alicia Mas (ORCID: https://orcid.org/0000-0001-8947-3207)
- Yinyi Yu
- Mathieu Thomas (ORCID: https://orcid.org/0000-0001-5803-9547)
- Getahun Abate (ORCID: https://orcid.org/0000-0002-7825-2422)
- Sokunthea Top
- Károly Tóth (ORCID: https://orcid.org/0000-0001-6624-9683)
- Franck Gallardo (ORCID: https://orcid.org/0000-0001-9341-826X)
- Eric M. Mucker (ORCID: https://orcid.org/0000-0002-4656-5379)
- Rekha G. Panchal (ORCID: https://orcid.org/0000-0001-8621-9078)
- Kelly S. Wetzel
- Janet Skerry
- Gaelle Frénois-Veyrat
- Alı́ Alejo (ORCID: https://orcid.org/0000-0002-1613-6063)
- Luigi A. Agrofoglio (ORCID: https://orcid.org/0000-0002-6083-0810)
- Cyril Colas (ORCID: https://orcid.org/0000-0003-1651-6813)
- Laetitia Boutin
- Rajini Mudhasani (ORCID: https://orcid.org/0000-0001-7824-6949)
- Estelle Mosca
- Vincent Roy (ORCID: https://orcid.org/0000-0002-1460-3932)
- Patrick Favetta (ORCID: https://orcid.org/0000-0002-5849-001X)
- Elie Marcheteau (ORCID: https://orcid.org/0000-0001-6630-9682)
- T. Garnier
Institutions
- Universidad Complutense de Madrid (ES)
- Université d'Orléans (FR)
- Consejo Superior de Investigaciones Científicas (ES)
- Université Paris-Saclay (FR)
- United States Army Medical Research Institute of Infectious Diseases (US)
- Technologies pour la Santé (FR)
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (ES)
- Laboratoire National de Référence (MA)
- UCLouvain Saint-Louis Brussels (BE)
- National Institute of Allergy and Infectious Diseases (US)
- Institut de Chimie Organique et Analytique (FR)
- Molecular Biology Consortium (US)
Publication Details
- Journal
- ACS Infectious Diseases
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1021/acsinfecdis.5c00169
- Citations
- 2
- Primary Topic
- Poxvirus research and outbreaks
- Type
- article
- Field-Weighted Citation Impact
- 2.07
Funders
- Agence Nationale de la Recherche
- Centre National de la Recherche Scientifique
- Université d'Orléans
- Direction Générale de l’Armement
- European Regional Development Fund
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases