Abstract
Dengue virus (DENV) that belongs to the Flavivirus genus, Flaviviridae family, represents the most important arbovirus causing human diseases. Based on serological test, four antigenically distinct serotypes are known: DENV-1, DENV-2, DENV-3 and DENV-4. Dengue can be presented in three clinical forms, undifferentiated febrile illness, dengue fever (DF) and dengue hemorrhagic fever with or without shock (DHF/DSS). The control of this infection is made by vector control, since there is no vaccine for protection neither any drug for treatment. Therefore, studies of new drugs for use against dengue are of great interest. The objective of this project is the evaluation of the potential antidengue (DENV-1, DENV-2, DENV-3 and DENV-4) activity of raw venom, fractions and molecules isolated from snakes (Bothrops jararacussu, B. pirajai, B. alternatus, B. moojeni B. atrox and Crotalus d. terrificus), scorpion (Tityus serrulatus), and frog (Bufo paracnemis). The antiviral effect of the toxins will be evaluated by in vitro and in vivo tests. VERO E6 cells will be used for the in vitro tests and the toxins antiviral activities will be evaluated before, during, and after cell infection. Those toxins showing antiviral effects in vitro will be evaluated in vivo using suckling mice (Swiss). The effect of the toxins over the DENV will be evaluated by replication inhibition, which will be measured by plaque lysis and/or real time RT-PCR assays. The antiviral activity will be determined associating the cytotoxic concentration that kill 50% of the cells monolayer (CC50) with the concentration that protect 50% of the cells monolayer of viral infection (CE50), based on these values, it will be calculated the selectivity index (IS=CC50/CE50), which expresses the potential antiviral activity of each toxin. (AU)
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