Antiviral Activity of the Acyclic Nucleoside Phosphonate Prodrug LAVR-289 against Poxviruses and African Swine Fever Virus

• DOI: 10.1021/acsinfecdis.5c00169
• Publication Date: 2025-05-22T08:17:57Z
• Authors: Elie Marcheteau; Estelle Mosca; Gaelle Frenois-Ve...; Sandrine Kappler-...; Laetitia Boutin; Sokunthea Top; Thomas Mathieu; Cyril Colas; Patrick Favetta; Tony Garnier; Peggy Barbe; Mathilde Keck; Daniel Gillet; Alicia Mas; Ali Alejo; Yinyi Yu; Karoly Toth; Getahun Abate; Vincent Roy; Janet Skerry; Kelly S Wetzel; Joshua D Shamblin; Joseph W Golden; Rekha G Panchal; Eric M Mucker; Rajini Mudhasani; Luigi A. Agrofoglio; Frederic Iseni; Franck Gallardo
• Keywords: Phosphonate; Nucleoside analogue

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 Asfarviridae family is not strictly classified as a Poxviridae member, both fall within same class of Pokkesviricetes that replicate in cytoplasm. Among compounds targeting these viruses, acyclic nucleoside phosphonate (ANP) prodrugs promising inhibitors viral polymerases. However, some limitations related their toxicity rapid emergence resistance highlight need for new antiviral molecules. In this study, we tested ANP called LAVR-289. This product effectively inhibits replication by specific domain poxvirus polymerase. Using monkeypox models, subcutaneous or oral administration LAVR-289 demonstrated protective efficacy infected animals without toxicity. Its vivo half-life, long on-the-shelf stability broad-spectrum make candidate further development stockpiling medical countermeasure against dsDNA outbreaks. can be positioned context recurrent epidemics, bioterrorism risk, resistant strains population.