Infection by one of the four serotypes of the arthropod-borne dengue virus produces a spectrum of disease manifestations, ranging from asymptomatic to life-threatening Dengue hemorrhagic fever/Dengue shock syndrome (DHF/DSS). During the last several decades, dengue has spread its geographic distribution to become the most common arboviral infection of humans in the subtropical and tropical regions of the world. There is no specific treatment or vaccine approved for human use. This fact, associated with the large number of infected individuals and the lack of markers that indicate which patients will develop severe disease, place an enormous burden on health systems of affected countries. Many efforts have been made to elucidate several aspects of dengue disease, but the pathogenesis of disease is complex and remains unclear. The hallmark of severe dengue disease is a short-lived plasma leakage that is believed to be immune mediated. Understanding the mechanism(s) that underlie the pathogenesis of dengue is critical for the development of safe therapeutics to prevent DHF/DSS. In this review, we highlight potential therapeutic alternatives to treat dengue infection and outline strategies used to develop and research anti-dengue therapies, focusing on in vivo results obtained using the experimental animal models currently available. Within this context, we discuss the therapeutic potential of novel antiviral molecules, either targeting virus-encoded functions or the cellular functions needed for viral replication. In addition, we discuss studies using anti-inflammatory strategies aimed at reducing the exacerbated host response against infection and their potential as promising therapeutic alternatives in severe dengue disease. Drug Dev Res 72:480-500, 2011. Key words: Dengue; therapeutics; animal models; inflammation; antiviral
DENGUE: OVERVIEWDengue is caused by a lipid-enveloped virus that contains a single-stranded, positive-sense RNA genome, the Dengue virus (DENV), which exists as four closely related serotypes (DENV-1-4). Dengue virus is a member of the Flaviviridae family and is related to the viruses that cause yellow fever and the Japanese, St. Louis, and West Nile encephalitides. As with other Flaviviruses, they are introduced into the host by an infected vector, Aedes aegypti and A. albopictus
DDRPublished online in Wiley Online Library (wileyonlinelibrary.com).