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Published online ahead of print on 4 November 2009 as doi:10.1099/vir.0.017269-0
J Gen Virol (2009), DOI 10.1099/vir.0.017269-0
© 2009 Society for General Microbiology

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Combinatorial chloroquine and ribavirin treatment does not prevent death in a hamster model of Nipah and Hendra virus infection

Alexander N Freiberg1, Melissa N Worthy1, Benhur Lee2 and Michael R Holbrook1,3

1 University of Texas Medical Branch;
2 University of California at Los Angeles

3 E-mail: mrholbro{at}utmb.edu

Hendra virus (HeV) and Nipah virus (NiV) are recently-emerged, closely related and highly pathogenic paramyxoviruses that cause severe disease, such as encephalitis, in animals and humans with fatality rates of up to 75%. Due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy they are classified as biosafety level 4 pathogens. A recent study reported that chloroquine, an anti-malarial drug, was effective in preventing NiV and HeV infection in cell culture experiments. In the present study we analyzed the antiviral efficacy of chloroquine, individually and in combination with ribavirin, in the treatment of NiV- and HeV-infection in in vivo experiments, using a golden hamster model. While we were able to confirm the strong antiviral activity of both drugs in inhibiting viral spread in vitro, they did not prove to be protective in the in vivo model. Ribavirin delayed death from viral disease in NiV-infected hamsters by approximately five days, but we did not observe any significant effect in HeV-infected hamsters. Chloroquine did not protect hamsters when administered either individually or in combination with ribavirin, the latter indicating lack of a favorable drug-drug interaction.

Received 30 September 2009; accepted 3 November 2009.





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