LAVR-289, an Orally Bioavailable Inhibitor of Adenovirus Replication <i>In Vitro</i> and <i>In Vivo</i>

Adenoviruses are responsible for a range of pathologies, including respiratory infections in children. Although most adenovirus infections are self-resolving, they can cause serious illness, particularly in immunocompromised individuals. There is currently no approved treatment for adenovirus infections. Here, we report on the antiviral activity of LAVR-289, a broad-spectrum acyclonucleoside phosphonate exhibiting potent <i>in vitro</i> efficacy against several adenovirus serotypes, comparable to that of brincidofovir. LAVR-289 specifically inhibits viral replication, blocking the formation of viral replication centers and preventing late protein expression without affecting viral entry or delivery of viral genomes to the nucleus. <i>In vivo</i>, using immunocompromised Syrian hamsters infected with HAdV-C6, oral administration of LAVR-289 resulted in 100% animal survival. These results suggest that LAVR-289 holds promise as a potential therapy for adenovirus infections paving the way for a future treatment of immunocompromised patients.