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Vaccination and Antiviral Treatment of Neglected Diseases Caused by Flaviviral Infections

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Abstract:

Flaviviral infections have a re-emerging impact on the health situation in developing countries with several billion of people living at risk. In the present review, we focus on three members of the genus Flavivirus belonging to the Flaviviridae family. They are transmitted to humans by mosquito bites, namely those viruses leading to Dengue Fever, Yellow Fever and mosquito-borne Japanese encephalitis. All three virus groups have a spherical structure with a diameter of approximately 50 nm. Although sharing a similar genomic structure and intracellular life cycle, they show different clinical manifestations. Infections are incurable, as there is no antiviral treatment available for either of the three viruses. Thus, prevention and vaccination are the best defenses. The most promising vaccines are live attenuated vaccines (LAVs), such as the YF17D strain against Yellow Fever or the SA-14-14-2 strain against Japanese encephalitis. Additionally, recombinant vaccines for Japanese encephalitis are in development. Although Dengue Fever is the most prevalent arthropode- borne flaviviral infection and a lot of research to develop a vaccine against all four Dengue Fever serotypes was undertaken, no vaccine is available on the market yet. Promising tetravalent vaccine candidates are currently undergoing clinical phase trials, including LAVs, recombinant and chimeric candidates as well as non-replicating vaccine approaches. Additionally, encouraging anti-flaviviral approaches target non-structural proteins, virus-specific proteases essential for cellular maturation of viral particles. Peptide inhibitors against the highly conserved NS2B and NS3 proteases are attractive as pan-flaviviral drug candidates.





Keywords: Aedes aegypti; Aedes albopictus; Aedes mosquitoes; Artemisia vulgaris; Chimeric LAVs; Culex tritaeniosphynchus; DENGUE VACCINE; Dengue Fever; ENDOPLASMATIC RETICU-LUM STRESS; Flaviviral infections; Flaviviral methyltransferases; Flaviviridae family; IMMUNE SYSTEM; Ixodes persulcatus; JAK-STAT SIGNALING PATH-WAY; Japanese Encephalitis; Lippia alba; Lippia origanoides; NITRIC OXIDE; NON-REPLICATING VACCINES; NS1; NS2A; NS2B; NS5 protein; NTPase; Oreganum vulgare; Recombinant LAVs; Vaccination; Viremia titers; World Health Organization; Yellow fever; antibodies; antibody-dependent enhancement; capsid protein (C); chimeras; colloid solutions; crystalloid; cyclophilins; dendritic cells; envelope protein (E); favipiravir; helicase; hemorrhagic fever; inosine monophosphate dehydrogenase (IMPDH); live attenuated vaccines; macrophages; membrane protein (prM/M); monocytes; open reading frame; peptidyl-prolyl isomerases; primary dog kidney (PDK); pyrazine carboxamide derivatives; recombinant vaccines; serine protease; signal transduction; sylvatic cycles; tetravalent vaccines; tick-borne encephalitis; triphosphatase; viral peptide inhibitors; xanthosine monophosphate; xodes ricinus

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986711794480168

Publication date: February 1, 2011

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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