Elsevier

Antiviral Research

Volume 83, Issue 3, September 2009, Pages 214-227
Antiviral Research

Review
Progress on the development of therapeutics against West Nile virus

https://doi.org/10.1016/j.antiviral.2009.05.006Get rights and content

Abstract

A decade has passed since the appearance of West Nile virus (WNV) in humans in the Western Hemisphere in New York City. During this interval, WNV spread inexorably throughout North and South America and caused millions of infections ranging from a sub-clinical illness, to a self-limiting febrile syndrome or lethal neuroinvasive disease. Its entry into the United States triggered intensive research into the basic biology of WNV and the elements that comprise a protective host immune response. Although no therapy is currently approved for use in humans, several strategies are being pursued to develop effective prophylaxis and treatments. This review describes the current state of knowledge on epidemiology, clinical presentation, pathogenesis, and immunobiology of WNV infection, and highlights progress toward an effective therapy.

Section snippets

Ecology, epidemiology, and clinical manifestations

West Nile virus (WNV) was first isolated in 1937 in the West Nile district of Uganda from a woman with an undiagnosed febrile illness (Smithburn et al., 1940). It is an RNA virus that cycles in nature between Culex mosquitoes and birds but also infects and causes disease in humans, horses, and other vertebrate species. Although its enzootic cycle was believed to be almost exclusively between mosquitoes and birds, with vertebrate species serving as “dead-end” hosts because of low-level and

Candidate anti-WNV therapeutics

At present, no specific therapy has been approved for use in humans with WNV infection as current treatment is supportive. Tissue culture and animal model studies have applied multiple strategies for the generation of novel therapies against WNV, and possibly other flaviviruses. Nonetheless, the development of therapeutics that mitigate or abort disease is challenging as patients with the most severe disease often have underlying immune deficits and present to clinical attention relatively late

Conclusions

Given the lack of existing therapies and its continued global emergence, the development of antiviral agents against WNV is essential. At present, several candidate therapies that act through distinct mechanisms are moving through various stages of pre-clinical development. Based on the epidemiology and pathogenesis of severe WNV infection effective antiviral agents against WNV must have minimal detrimental effects on immune system function. Even with the identification of new classes of

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