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Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus
Molecular Virology Branch, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21772, USA
Department of Microbiology and Immunology, Center for Predictive Medicine for Infectious Diseases and Biodefense, Louisville, KY 40202, USA
* Authors to whom correspondence should be addressed.
Received: 5 September 2013; in revised form: 23 October 2013 / Accepted: 31 October 2013 / Published: 8 November 2013
Abstract: 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.
Keywords: hantaviruses; ribavirin; hamster; prophylactic; post-exposure antiviral
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MDPI and ACS Style
Ogg, M.; Jonsson, C.B.; Camp, J.V.; Hooper, J.W. Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus. Viruses 2013, 5, 2704-2720.
Ogg M, Jonsson CB, Camp JV, Hooper JW. Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus. Viruses. 2013; 5(11):2704-2720.
Ogg, Monica; Jonsson, Colleen B.; Camp, Jeremy V.; Hooper, Jay W. 2013. "Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus." Viruses 5, no. 11: 2704-2720.