| Texto completo | |
| Autor(es): |
Verde Bastos Borba, Joyce Villa
;
Silva, Arthur de Carvalho E.
;
do Nascimento, Marilia Nunes
;
Ferreira, Leticia Tiburcio
;
Rimoldi, Aline
;
Starling, Luisa
;
Pereira Ramos, Pablo Ivan
;
Maranhao Costa, Fabio Trindade
;
Andrade, Carolina Horta
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL; v. 20, p. 10-pg., 2022-07-15. |
| Resumo | |
Malaria is a tropical disease caused by Plasmodium spp. and transmitted by the bite of infected Anopheles mosquitoes. Protein kinases (PKs) play key roles in the life cycle of the etiological agent of malaria, turning these proteins attractive targets for antimalarial drug discovery campaigns. As part of an effort to understand parasite signaling functions, we report the results of a bioinformatics pipeline analysis of PKs of eight Plasmodium species. To date, no P. malariae and P. ovale kinome assemble has been conducted. We classified, curated and annotated predicted kinases to update P. falciparum, P. vivax, P. yoelii, P. berghei, P. chabaudi, and P. knowlesi kinomes published to date, as well as report for the first time the kinomes of P. malariae and P. ovale. Overall, from 76 to 97 PKs were identified among all Plasmodium spp. kinomes. Most of the kinases were assigned to seven of nine major kinase groups: AGC, CAMK, CMGC, CK1, STE, TKL, OTHER; and the Plasmodium-specific group FIKK. About 30% of kinases have been deeply classified into group, family and subfamily levels and only about 10% remained unclassified. Furthermore, updating and comparing the kinomes of P. vivax and P. falciparum allowed for the prioritization and selection of kinases as potential drug targets that could be explored for discovering new drugs against malaria. This integrated approach resulted in the selection of 37 protein kinases as potential targets and the identification of investigational compounds with moderate in vitro activity against asexual P. falciparum (3D7 and Dd2 strains) stages that could serve as starting points for the search of potent antimalarial leads in the future. (C) 2022 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. (AU) | |
| Processo FAPESP: | 19/21854-4 - Priorização de quinases e descoberta de compostos com atividade antimalárica contra diferentes estágios de Plasmodium vivax utilizando ferramentas de quimiogenômica, bioinformática, quimioinformática e ensaios experimentais |
| Beneficiário: | Joyce Villa Verde Bastos Borba |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 20/02158-4 - Identificação de moléculas com ação hipnozonticida baseada em análises de quimiogenômica, bioinformática e fenotípicas: enfoque em Plasmodium vivax |
| Beneficiário: | Aline Rimoldi Ribeiro |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 19/02171-3 - Investigação da atividade antimalárica e de alvos moleculares de compostos naturais identificados por quimioinformática contra Plasmodium vivax |
| Beneficiário: | Letícia Tiburcio Ferreira |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |