Arsenic trioxide influences viral replication in target organs of coxsackievirus B3-infected mice

Abstract

New antiviral agents are urgently needed. Based on in vitro studies, arsenic trioxide (As₂O₃) seems to affect viral replication, although this has been studied only marginally in vivo. In this study the replication of coxsackievirus B3 (CVB3) was studied in Balb/c mice administered 1 mg As₂O₃/kg bw once daily during 7 days of infection and in Vero cells exposed for 3 or 5 days to 0.4, 2 or 4 μM As₂O₃. Viral RNA was measured by reverse transcription PCR (RT-PCR) (in vitro and in vivo) and arsenic concentration was measured by inductively coupled plasma-mass spectrometry (ICP-MS) (in vivo). In vivo, As₂O₃ decreased viral RNA in the brain on days 3 (by 81%; p < 0.05) and 7 (by 97%; p < 0.01) and in the pancreas on day 7 (by 75%; p < 0.05), two of the target organs of this infection. The results were confirmed in vitro, where As₂O₃ dose-dependently reduced viral RNA, with the effect being more pronounced in the surrounding culture medium than inside the infected cells, indicating an impaired virion release. Thus, As₂O₃ reduced CVB3 replication both in vitro and in vivo, indicating that As₂O₃ is a viable option in the pursuit of new therapeutic agents against viral infections.