DERT Annual Scientific Retreat

The potential use of variola virus, the causative agent of smallpox, as a bioweapon and the endemic presence of monkeypox virus in Africa demonstrate the need for better therapies for orthopoxvirus infections. Chemotherapeutic approaches to control viral infections have been less successful than those targeting bacterial infections. While bacteria commonly reproduce themselves outside of cells and have metabolic functions against which antibiotics can be directed, viruses replicate in the host cells using the cells' metabolic pathways. This makes it very difficult to selectively target the virus without damaging the host. Therefore, the development of antiviral drugs against poxviruses has initially focused on unique properties of the viral replication cycle or of viral proteins that can be selectively targeted. However, recent advances in molecular biology have provided insights into host factors that represent novel drug targets. The latest anti-poxvirus drugs are kinase inhibitors, which were originally developed to treat cancer progression but in addition block egress of poxviruses from infected cells. This review will summarize the current understanding of anti-poxvirus drugs and will give an overview of the development of the latest second generation poxvirus drugs. Background The worldwide eradication of the naturally occurring smallpox virus, variola, in 1980 resulted in a decreased demand for the development of therapies [1]. Due to recent worldwide political developments, variola is nowadays widely regarded as one of the most significant bioterrorist threats, reestablishing the need for efficient therapy for poxvirus infection [2,3]. The impact of a smallpox virus attack in the human population today would be even more catastrophic than during the last century, since the vaccination programs were suspended worldwide around 1976 [4]. The lethality of the disease (up to 40%) and its ease of transmissibility have prompted the CDC (Center for Disease Control and Prevention), an agency recognized as the leading United States government agency for protecting public health and safety, to place variola virus at the top of the high-threat (Category A) agents list [5]. In addition to the bioweapon threat, there is a natural public threat arising from monkeypox virus, a virus that produces a disease in man that closely resembles smallpox. Monkeypox exists naturally in western and central Africa, but 72 cases were also reported in the United States in 2003 [2,6,7]. Variola and monkeypox viruses belong to the family of poxviridae, which consists of a collection of large, enveloped, double-stranded DNA viruses that are distinguishable by their unique morphology and cytoplasmic site of Published: 15 January 2007 Virology Journal 2007, 4:8 doi:10.1186/1743-422X-4-8 Received: 10 January 2007 Accepted: 15 January 2007 This article is available from: http://www.virologyj.com/content/4/1/8 © 2007 Sliva and Schnierle; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.