Malaria is one of the most important public health problems in tropical and subtropical areas, with approximately 200 million cases worldwide annually. In Brazil, P. vivax is the most prevalent species, accounting for around 85% of all cases, and reports of severe cases associated with P. vivax have been increasing in the last few years. In absence of an effective vaccine, rapid treatment is essential to malaria control. However, parasite resistance to currently available compounds highlights the urgent need for identifying new antimalarial therapies. In this context, the present project's main objective is to identify compounds against molecular targets whose inhibition may impair growth of sexual and asexual blood stages of P. vivax. At first, a comparative genomics strategy will be applied to select protein kinases that are essential for P. vivax and P. falciparum development, but absent or with low similarity in humans. Subsequently, using homology modelling and molecular docking, virtual screening will be performed in kinase inhibitor library (Biofocus). Compounds displaying in silico inhibitory potential will then be evaluated in functional assays. Initially, the compounds will be tested in in vitro assays with P. falciparum and in vivo using the experimental model of malaria P. chabaudi. Next, that compounds that display good inhibitory activity will be evaluated in ex vivo assays with P. vivax isolates from the Amazon. In conclusion, the present project could help to identify new antimalarial therapies, especially against vivax malaria.
News published in Agência FAPESP Newsletter about the scholarship:
FERREIRA, LETICIA TIBURCIO;
CASSIANO, GUSTAVO CAPATTI;
TAVELLA, TATYANA ALMEIDA;
PERALIS TOMAZ, KAIRA CRISTINA;
BAIA-DA-SILVA, DJANE CLARYS;
SOUZA, MACEJANE FERREIRA;
DO NASCIMENTO LIMA, MARILIA NUNES;
ALMEIDA, LUDIMILA DIAS;
SILVA DE BARROS PUCA, MARIA CAROLINA;
MELO, GISELY CARDOSO;
BARGIERI, DANIEL YOUSSEF;
PINTO LOPES, STEFANIE COSTA;
GUIMARAES LACERDA, MARCUS VINICIUS;
NEVES, BRUNO JUNIOR;
ANDRADE, CAROLINA HORTA;
LEMOS CRAVO, PEDRO VITOR;
MARANHAO COSTA, FABIO TRINDADE.
Computational Chemogenomics Drug Repositioning Strategy Enables the Discovery of Epirubicin as a New Repurposed Hit for Plasmodium falciparum and P. vivax.
Antimicrobial Agents and Chemotherapy,
Web of Science Citations: 1.