Molecular Virology Branch, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21772, USA.
Viruses. 2013 Nov 8;5(11):2704-20. doi: 10.3390/v5112704.
Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route.
安第斯病毒（ANDV）由野生啮齿动物携带，在传播给人类后会引起高度致命的汉坦病毒肺综合征（HPS），导致 30%至 50%的病例死亡。由于目前尚无针对这种疾病的治疗方法，我们系统地测试了利巴韦林在体外和动物模型中的疗效。体外检测证实了其抗病毒活性，并确定最有效的剂量为 40μg/ml 及以上。我们在 ANDV 仓鼠模型中测试了三种不同浓度的利巴韦林，以检测其在鼻腔接种后预防 HPS 的能力。虽然最高浓度（200mg/kg）的利巴韦林对仓鼠有毒性，但中浓度（100mg/kg）和低浓度（50mg/kg）均能预防仓鼠的 HPS 且无毒性。具体来说，对于这两个组，所有 8 只仓鼠在鼻腔接种后均存活，而 8 只 PBS 对照处理的动物中有 7 只发展为致命性 HPS。此外，我们报告称，在感染后第 6、8、10 或 12 天开始每天给予 50mg/kg 的利巴韦林治疗可显著预防所有组的 HPS。在感染后 14 天给予利巴韦林也能提供显著水平的预防致命性 HPS 的保护。这些数据为利巴韦林作为呼吸道暴露后预防 HPS 的暴露后治疗提供了体内证据支持。
