Update and elucidation of Plasmodium kinomes: prioritization of kinases as potential drug targets for malaria

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dc.creatorBorba, Joyce Villa Verde Bastos
dc.creatorSilva, Arthur de Carvalho e
dc.creatorNascimento, Marília Nunes do
dc.creatorFerreira, Letícia Tiburcio
dc.creatorRibeiro, Aline Rimoldi
dc.creatorStarling, Luísa Caldas
dc.creatorRamos, Pablo Ivan Pereira
dc.creatorCosta, Fabio Trindade Maranhão
dc.creatorAndrade, Carilona Horta
dc.date.accessioned2024-11-19T13:10:23Z
dc.date.available2024-11-19T13:10:23Z
dc.date.issued2022
dc.description.abstractMalaria 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.
dc.identifier.citationBORBA, Joyce Villa Verde Bastos et al. Update and elucidation of plasmodium kinomes: prioritization of kinases as potential drug targets for malaria. Computational and Structural Biotechnology Journal, Amsterdam, v. 20, p. 3708-3717, 2022. DOI: 10.1016/j.csbj.2022.07.003. Disponível em: https://www.sciencedirect.com/science/article/pii/S2001037022002835. Acesso em: 21 out. 2024.
dc.identifier.doi10.1016/j.csbj.2022.07.003
dc.identifier.issne- 2001-0370
dc.identifier.urihttp://repositorio.bc.ufg.br//handle/ri/25920
dc.language.isoeng
dc.publisher.countryHolanda
dc.publisher.departmentFaculdade de Farmácia - FF (RMG)
dc.rightsAcesso Aberto
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectPlasmodium
dc.subjectProtein kinase
dc.subjectMalaria
dc.subjectKinome
dc.subjectTarget prioritization
dc.subjectDrug discovery
dc.titleUpdate and elucidation of Plasmodium kinomes: prioritization of kinases as potential drug targets for malaria
dc.typeArtigo

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