Targeting malaria protein kinases

Author(s)

Cassiano, G. C. ; Tavella, T. A. ; Nascimento, M. N. ; Rodrigues, D. A. ; Cravo, P. V. L. ; Andrade, Carolina Horta ; Maranhao Costa, Fabio Trindade ; Donev, R

• Document type: Journal article
• Source: ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY, VOL 124: PROTEIN KINASES IN DRUG DISCOVERY; v. 124, p. 50-pg., 2021-01-01.

Abstract

Malaria is one of the most impacting public health problems in tropical and subtropical areas of the globe, with approximately 200 million cases worldwide annually. In the absence of an effective vaccine, rapid treatment is vital for effective malaria control. However, parasite resistance to currently available drugs underscores the urgent need for identifying new antimalarial therapies with new mechanisms of action. Among potential drug targets for developing new antimalarial candidates, protein kinases are attractive. These enzymes catalyze the phosphorylation of several proteins, thereby regulating a variety of cellular processes and playing crucial roles in the development of all stages of the malaria parasite life cycle. Moreover, the large phylogenetic distance between Plasmodium species and its human host is reflected in marked differences in structure and function of malaria protein kinases between the homologs of both species, indicating that selectivity can be attained. In this review, we describe the functions of the different types of Plasmodium kinases and highlight the main recent advances in the discovery of kinase inhibitors as potential new antimalarial drug candidates. (AU)

• FAPESP's process: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax
• Grantee: Fabio Trindade Maranhão Costa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/27626-3 - Identification of new antimalarial compounds for target-centered drug repositioning approach
• Grantee: Tatyana Almeida Tavella
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/20774-6 - Identifying protein kinase inhibitors as antimalarial agents using chemogenomic, bioinfomatics and phenotypic strategies: focus in Plasmodium vivax.
• Grantee: Gustavo Capatti Cassiano
• Support Opportunities: Scholarships in Brazil - Post-Doctoral