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This Article Full Text (Papers in Press[PDF]) All Versions of this Article: vir.0.017269-0v1 91/3/765    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Freiberg, A. N Articles by Holbrook, M. R PubMed PubMed Citation Articles by Freiberg, A. N Articles by Holbrook, M. R Agricola Articles by Freiberg, A. N Articles by Holbrook, M. R

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

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.