Infectious Diseases, Department of Medical Sciences, Uppsala University Hospital, S-751 85 Uppsala, Sweden.
Microbes Infect. 2010 Nov;12(12-13):1027-34. doi: 10.1016/j.micinf.2010.07.003. Epub 2010 Jul 16.
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.
急需新型抗病毒药物。基于体外研究，三氧化二砷（As₂O₃）似乎能影响病毒复制，尽管其在体内的研究还很有限。本研究在给予感染期内每日 1 毫克/公斤体重三氧化二砷（As₂O₃）的 Balb/c 小鼠及暴露于 0.4、2 或 4 μM As₂O₃ 的 Vero 细胞中，研究了柯萨奇病毒 B3（CVB3）的复制。通过逆转录 PCR（RT-PCR）（体外和体内）测量病毒 RNA，通过电感耦合等离子体质谱（ICP-MS）（体内）测量砷浓度。在体内，三氧化二砷（As₂O₃）在第 3 天（减少 81%；p < 0.05）和第 7 天（减少 97%；p < 0.01）降低了大脑中的病毒 RNA，以及第 7 天降低了胰腺中的病毒 RNA（减少 75%；p < 0.05），这两个都是这种感染的靶器官。该结果在体外得到了证实，三氧化二砷（As₂O₃）呈剂量依赖性地降低了病毒 RNA，在周围培养基中的作用比感染细胞内更明显，表明病毒粒子释放受损。因此，三氧化二砷（As₂O₃）在体内和体外均降低了 CVB3 的复制，表明三氧化二砷（As₂O₃）是一种有前途的新型抗病毒药物。
