Artesunate derivative TF27 inhibits replication and pathogenesis of an oncogenic avian alphaherpesvirus

Nucleoside analogues have been the cornerstone of clinical treatment of herpesvirus infections since the 1970s. However, severe side effects and emergence of drug resistant viruses raise the need for alternative treatment options. We recently investigated the broad and strong antiherpesviral activity of the optimized artesunate derivative TF27 in vitro. TF27 efficiently inhibited replication of the highly oncogenic Marek's disease virus (MDV), a virus that infects chickens, causes deadly lymphomas and threatens poultry populations worldwide. In this study, we used this natural virus-host model for herpesvirus-induced cancer by infecting chickens with MDV, and evaluated the protective efficacy of TF27 and the nucleoside analogue valganciclovir (VGCV) on virus replication and tumorigenesis. We could demonstrate that both drugs reduced viral load in the blood and prevented tumor development in a large portion of the animals. Antiviral treatment also had a positive impact on body weight gain, while no negative compound-associated side effects were observed. This research provides the first evidence that the artesunate derivative TF27 and VGCV can be used in avian species and that they inhibit MDV replication and tumorigenesis. In addition, our study paves the way for promising approaches in future antiherpesviral drug development. •Artesunate and its derivatives are an abundant source for lead compounds and drug candidates in antiviral drug development.•Trimeric artesunate-derived NF-κB inhibitor TF27 impairs replication of the oncogenic Marek's disease virus.•TF27 inhibits lymphoma formation without compound-associated side effects.•Our findings open new chances for future medical use of this experimental antiherpesviral drug candidate.