IN-VITRO EVALUATION OF A-5021 ANTI-VIRAL ACTIVITY AGAINST TESTUDINID HERPESVIRUS 3 AND INITIAL PHARMACOKINETIC STUDY IN HERMANN'S TORTOISE (Testudo hermanni)

Testudinid herpesvirus infections in tortoises belonging to the Testudinidae family are well known for decades, but their pathogenesis remains poorly understood and treatments are often empirical. This study describes the in vitro evaluation of selected anti-herpesvirus compounds against Testudinid Herpesvirus 3 (THV-3). A-5021, a compound with known broad-spectrum anti-herpetic activity, showed to be 9 times more potent than acyclovir, with an EC50 of 13.2 µM and inducing a complete inhibition of viral replication at 37.7 µM. Initial pharmacokinetic parameters were determined after a single sub-cutaneous administration of 5 and 10 mg/kg in Hermann’s tortoises (Testudo hermanni, n=3). Blood samples were collected at different time points and plasma concentrations of A-5021 were determined. No adverse effects were clinically observed and plasma concentrations remained above the EC50 for 2.8 and 4.2 h after administration of 5 and 10 mg/kg, respectively. These preliminary data provide a basis for further proof-of-concept studies for a potential prophylactic or therapeutic treatment of THV-3 infection in tortoises