New directions in antimalarial target validation

Author(s)

Batista, Fernando A. ^{[1, 2]} ; Gyau, Benjamin ^[2] ; Vilacha, Juliana F. ^[2] ; Bosch, Soraya S. ^{[1, 2]} ; Lunev, Sergey ^[2] ; Wrenger, Carsten ^[1] ; Groves, Matthew R. ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Unit Drug Discovery, Sao Paulo - Brazil

^[2] Univ Groningen, Dept Pharm, Struct Biol Unit, XB20 Drug Design, Groningen - Netherlands

• Document type: Review article
• Source: EXPERT OPINION ON DRUG DISCOVERY; v. 15, n. 2, p. 189-202, FEB 1 2020.
• Web of Science Citations: 0

Abstract

Introduction: Malaria is one of the most prevalent human infections worldwide with over 40% of the world's population living in malaria-endemic areas. In the absence of an effective vaccine, emergence of drug-resistant strains requires urgent drug development. Current methods applied to drug target validation, a crucial step in drug discovery, possess limitations in malaria. These constraints require the development of techniques capable of simplifying the validation of Plasmodial targets. Areas covered: The authors review the current state of the art in techniques used to validate drug targets in malaria, including our contribution - the protein interference assay (PIA) - as an additional tool in rapid in vivo target validation. Expert opinion: Each technique in this review has advantages and disadvantages, implying that future validation efforts should not focus on a single approach, but integrate multiple approaches. PIA is a significant addition to the current toolset of antimalarial validation. Validation of aspartate metabolism as a druggable pathway provided proof of concept of how oligomeric interfaces can be exploited to control specific activity in vivo. PIA has the potential to be applied not only to other enzymes/pathways of the malaria parasite but could, in principle, be extrapolated to other infectious diseases. (AU)

• FAPESP's process: 17/03966-4 - Targeting lipoic acid salvage and biosynthesis pathways in MRSA
• Grantee: Carsten Wrenger
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
• Grantee: Carsten Wrenger
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/17577-9 - Analysis of the ATCase catalysis within the amino acid metabolism of the human malaria parasite Plasmodium falciparum
• Grantee: Soraya Soledad Bosch
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)