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Novel therapeutic weapons against poxviruses Volume 12, issue 5, Septembre-Octobre 2008

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Authors
Institut Rega, Section virologie et chimiothérapie, Minderbroedersstraat 10, 3000 Leuven, Belgique

Poxviruses include several pathogens responsible for diseases recognized as important for human health, such as smallpox, monkeypox, orf and molluscum contagiosum. Smallpox, whose etiological agent is Variola virus, is a highly contagious disease which was eradicated last century. Today, the potential use of Variola virus in bioterrorism is real. Hence, efforts have been intensified for the selection of novel anti-poxvirus compounds. The increased understanding of the poxviral replication, the establishment of three-dimensional cell cultures, as well as the validation of several animal models, have led to the discovery and the development of new and promising classes of compounds active against poxviruses. Cidofovir, an acyclic cytosine phosphonate analogue and hexadecylpropanediol-cidofovir (CMX001), one of its prodrug orally bioavailable, inhibit poxvirus replication in vitro, ex vivo and in vivo by targeting the viral DNA polymerase. Another compound, ST-246, inhibits a crucial step of the orthopoxvirus morphogenesis. Its antiviral activity has been demonstrated in several animal models, and its safety has been confirmed in healthy human volunteers following a phase I clinical trial. Recent developments made in vitro, ex vivo, in vivo and in humans, in terms of antiviral treatments available of poxvirus infections, are discussed in this review.