Identification of kinase inhibitors with antimalarial activity based on chemogenomics, bioinformatics and phenotypic analyzes: focus on Plasmodium vivax

Malaria remains a serious public health problem in many tropical and subtropical regions, with approximately 200 million cases annually worldwide. In Brazil, Plasmodium vivax is the main species, responsible for approximately 85% of cases, and reports of clinical complications associated with this species have been observed. In the absence of an effective vaccine, immediate treatment is the main measure to combat the disease. However, with the recurrent evolution of resistance of the parasite to the antimalarials used, the need to develop new treatments becomes evident. First, a comparative genomics strategy will be applied to select essential protein kinases for the development of P. vivax and P. falciparum, but which have low similarity with human kinases. Subsequently, using homology modeling and docking, a virtual screening will be performed on a library of compounds focused on kinases (Biofocus), and those compounds with inhibitory potential will have their antimalarial activities determined through functional assays. Initially, the compounds will be evaluated in in vitro assays with P. falciparum and in vivo using the experimental infection model with P. chabaudi. Subsequently, compounds that demonstrate good efficacy in the initial phenotypic assays will be tested ex vivo on P. vivax isolates in the Amazon. Thus, the proposal aims to contribute to the identification of new therapeutic alternatives for the treatment of malaria, especially vivax.

Project Details

Drug-based Strategies
P. vivax
Product Development

Sep 2018 — Sep 2019

Brazil