Acyclic Nucleoside Phosphonate Prodrug LAVR-289 Inhibits Marek's Disease Virus Replication

Since the 1970s, numerous antivirals targeting human herpesviruses have been developed, yet their application in veterinary medicine remains limited due to poor bioavailability and significant toxicity in animals. Recently, LAVR-289, a novel acyclic nucleoside phosphonate analogue, has demonstrated broad-spectrum antiviral activity against various DNA viruses. In the present study, we investigated the antiviral potential of LAVR-289 against Marek's disease virus (MDV), an avian herpesvirus responsible for a fatal lymphoproliferative disease in chickens and substantial economic losses to the poultry industry. Using two different avian cell culture infection models, we showed that LAVR-289 potently inhibited MDV replication at nanomolar concentrations, leading to a marked reduction in both the number and size of virus-induced plaques. Importantly, LAVR-289 exhibited minimal cytotoxicity in the treated cell cultures. Further analyses also revealed that LAVR-289 was effective at both early and late stages of MDV infection, and its antiviral activity was maintained under oxygen levels close to physiological conditions. Taken together, these findings highlight LAVR-289 as a promising antiviral drug against MDV and potentially other avian DNA viruses.