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Evaluation of the in vivo antiviral activity and identification of the target(s) of crotoxin and PLA2-CB, isolated from Caudisona durissa terrificus, in the inhibition of Dengue and Yellow Fever viruses replication

Grant number: 11/19227-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2011
Effective date (End): November 30, 2013
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Victor Hugo Aquino Quintana
Grantee:Vanessa Danielle Menjon Müller
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Dengue is the most important arbovirus disease in the world; nearly 50 million infections occur annually resulting in 500,000 cases of dengue hemorrhagic fever and 22,000 deaths. Yellow fever is a viral hemorrhagic fever with high mortality rate. Although there is an effective vaccine against yellow fever, about 200,000 cases of yellow fever still occur annually, mainly in Africa. Thus, the development of antiviral drugs against these viruses should be a public health priority. Natural products of plant or animal origin have an extensive chemical diversity, and an inexhaustible source of compounds with promising biological activities. During my doctorate thesis, we evaluated the antiviral activity of toxins isolated from Caudisona durissa terrificus snake venom against dengue viruses (DENV) and yellow fever virus (YFV). Crotoxin and PLA2-CB were the toxins that showed the highest inhibitory activity for both viruses, mainly in the early phases of the viral replication cycle. However, it was not possible to identify the target(s) of these toxins. The aim of this study is to identify the target(s) of crotoxin and PLA2-CB in the DENV and YFV replication inhibition, and to evaluate the effect of these toxins in an in vivo experimental model.