Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malaria
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 pa...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
|
| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022002835 |
| _version_ | 1797978206356111360 |
|---|---|
| author | Joyce Villa Verde Bastos Borba Arthur de Carvalho e Silva Marília Nunes do Nascimento Letícia Tiburcio Ferreira Aline Rimoldi Luísa Starling Pablo Ivan Pereira Ramos Fabio Trindade Maranhão Costa Carolina Horta Andrade |
| author_facet | Joyce Villa Verde Bastos Borba Arthur de Carvalho e Silva Marília Nunes do Nascimento Letícia Tiburcio Ferreira Aline Rimoldi Luísa Starling Pablo Ivan Pereira Ramos Fabio Trindade Maranhão Costa Carolina Horta Andrade |
| author_sort | Joyce Villa Verde Bastos Borba |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T05:19:18Z |
| format | Article |
| id | doaj.art-350ff42426ea4ae4a76374f2cc7f5835 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:19:18Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-350ff42426ea4ae4a76374f2cc7f58352022-12-24T04:53:19ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012037083717Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malariaJoyce Villa Verde Bastos Borba0Arthur de Carvalho e Silva1Marília Nunes do Nascimento2Letícia Tiburcio Ferreira3Aline Rimoldi4Luísa Starling5Pablo Ivan Pereira Ramos6Fabio Trindade Maranhão Costa7Carolina Horta Andrade8LabMol – Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás (UFG), Goiânia, Brazil; Laboratory of Tropical Diseases – Prof. Dr. Luiz Jacintho da Silva, Department of Genetics Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, BrazilLabMol – Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás (UFG), Goiânia, BrazilLabMol – Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás (UFG), Goiânia, BrazilLaboratory of Tropical Diseases – Prof. Dr. Luiz Jacintho da Silva, Department of Genetics Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, BrazilLaboratory of Tropical Diseases – Prof. Dr. Luiz Jacintho da Silva, Department of Genetics Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, BrazilLabMol – Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás (UFG), Goiânia, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, BrazilLaboratory of Tropical Diseases – Prof. Dr. Luiz Jacintho da Silva, Department of Genetics Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil; Corresponding authors at: LabMol - Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Rua 240, Qd. 87, St. Leste Universitário, Goiânia - GO, 74605-170, Brazil (C.H. Andrade). Laboratory of Tropical Diseases – Prof. Dr. Luiz Jacintho da Silva, Laboratory of Tropical Diseases Dep. Genetics, Evolution, Microbiology and ImmunologyInstitute of Biology, Rua Carl Von Linnaeus, 2-238, 13083-864, Campinas-SP, Brazil (F.T.M. Costa).LabMol – Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás (UFG), Goiânia, Brazil; Laboratory of Tropical Diseases – Prof. Dr. Luiz Jacintho da Silva, Department of Genetics Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil; Corresponding authors at: LabMol - Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Rua 240, Qd. 87, St. Leste Universitário, Goiânia - GO, 74605-170, Brazil (C.H. Andrade). Laboratory of Tropical Diseases – Prof. Dr. Luiz Jacintho da Silva, Laboratory of Tropical Diseases Dep. Genetics, Evolution, Microbiology and ImmunologyInstitute of Biology, Rua Carl Von Linnaeus, 2-238, 13083-864, Campinas-SP, Brazil (F.T.M. Costa).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.http://www.sciencedirect.com/science/article/pii/S2001037022002835PlasmodiumProtein kinaseMalariaKinomeTarget prioritizationDrug discovery |
| spellingShingle | Joyce Villa Verde Bastos Borba Arthur de Carvalho e Silva Marília Nunes do Nascimento Letícia Tiburcio Ferreira Aline Rimoldi Luísa Starling Pablo Ivan Pereira Ramos Fabio Trindade Maranhão Costa Carolina Horta Andrade Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malaria Computational and Structural Biotechnology Journal Plasmodium Protein kinase Malaria Kinome Target prioritization Drug discovery |
| title | Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malaria |
| title_full | Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malaria |
| title_fullStr | Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malaria |
| title_full_unstemmed | Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malaria |
| title_short | Update and elucidation of Plasmodium kinomes: Prioritization of kinases as potential drug targets for malaria |
| title_sort | update and elucidation of plasmodium kinomes prioritization of kinases as potential drug targets for malaria |
| topic | Plasmodium Protein kinase Malaria Kinome Target prioritization Drug discovery |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022002835 |
| work_keys_str_mv | AT joycevillaverdebastosborba updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria AT arthurdecarvalhoesilva updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria AT marilianunesdonascimento updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria AT leticiatiburcioferreira updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria AT alinerimoldi updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria AT luisastarling updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria AT pabloivanpereiraramos updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria AT fabiotrindademaranhaocosta updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria AT carolinahortaandrade updateandelucidationofplasmodiumkinomesprioritizationofkinasesaspotentialdrugtargetsformalaria |