| Full text | |
| Author(s): |
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
Total Authors: 9
|
| Document type: | Journal article |
| Source: | COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL; v. 20, p. 10-pg., 2022-07-15. |
| Abstract | |
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) | |
| FAPESP's process: | 19/21854-4 - Kinase prioritization and discovery of compounds with anti-malarial activity against different stages of Plasmodium vivax using chemogenomics, bioinformatics, cheminformatics, and experimental evaluation tools |
| Grantee: | Joyce Villa Verde Bastos Borba |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 20/02158-4 - Identifying hypnozonticidal agents using chemogenomic, bioinfomatics and phenotypic strategies: focus in Plasmodium vivax |
| Grantee: | Aline Rimoldi Ribeiro |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/02171-3 - Investigation of antimalarial activity and molecular targets of natural compounds identified by chemoinformatics against Plasmodium vivax |
| Grantee: | Letícia Tiburcio Ferreira |
| Support Opportunities: | Scholarships in Brazil - Doctorate |