Publication

New directions in antimalarial target validation

Batista, F. A., Gyau, B., Vilacha, J. F., Bosch, S. S., Lunev, S., Wrenger, C. & Groves, M. R., 1-Feb-2020, In : Expert Opinion on Drug Discovery. 15, 2, p. 189-202 14 p.

Research output: Contribution to journalReview articleAcademicpeer-review

APA

Batista, F. A., Gyau, B., Vilacha, J. F., Bosch, S. S., Lunev, S., Wrenger, C., & Groves, M. R. (2020). New directions in antimalarial target validation. Expert Opinion on Drug Discovery, 15(2), 189-202. https://doi.org/10.1080/17460441.2020.1691996

Author

Batista, Fernando A ; Gyau, Benjamin ; Vilacha, Juliana F ; Bosch, Soraya S ; Lunev, Sergey ; Wrenger, Carsten ; Groves, Matthew R. / New directions in antimalarial target validation. In: Expert Opinion on Drug Discovery. 2020 ; Vol. 15, No. 2. pp. 189-202.

Harvard

Batista, FA, Gyau, B, Vilacha, JF, Bosch, SS, Lunev, S, Wrenger, C & Groves, MR 2020, 'New directions in antimalarial target validation', Expert Opinion on Drug Discovery, vol. 15, no. 2, pp. 189-202. https://doi.org/10.1080/17460441.2020.1691996

Standard

New directions in antimalarial target validation. / Batista, Fernando A; Gyau, Benjamin; Vilacha, Juliana F; Bosch, Soraya S; Lunev, Sergey; Wrenger, Carsten; Groves, Matthew R.

In: Expert Opinion on Drug Discovery, Vol. 15, No. 2, 01.02.2020, p. 189-202.

Research output: Contribution to journalReview articleAcademicpeer-review

Vancouver

Batista FA, Gyau B, Vilacha JF, Bosch SS, Lunev S, Wrenger C et al. New directions in antimalarial target validation. Expert Opinion on Drug Discovery. 2020 Feb 1;15(2):189-202. https://doi.org/10.1080/17460441.2020.1691996


BibTeX

@article{af981d6a2596437382f2ea974e442613,
title = "New directions in antimalarial target validation",
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.",
keywords = "Protein oligomerisation, malaria, drug target validation, phenotypic mapping, FALCIPARUM DIHYDROOROTATE DEHYDROGENASE, PLASMODIUM-VIVAX DHFR, MALARIA PARASITES, DRUG TARGET, PIPERAQUINE RESISTANCE, TRANSGENE EXPRESSION, NEGATIVE SELECTION, LEAD OPTIMIZATION, GENE-EXPRESSION, BLOOD STAGES",
author = "Batista, {Fernando A} and Benjamin Gyau and Vilacha, {Juliana F} and Bosch, {Soraya S} and Sergey Lunev and Carsten Wrenger and Groves, {Matthew R}",
year = "2020",
month = "2",
day = "1",
doi = "10.1080/17460441.2020.1691996",
language = "English",
volume = "15",
pages = "189--202",
journal = "Expert Opinion on Drug Discovery",
issn = "1746-0441",
publisher = "Taylor & Francis Group",
number = "2",

}

RIS

TY - JOUR

T1 - New directions in antimalarial target validation

AU - Batista, Fernando A

AU - Gyau, Benjamin

AU - Vilacha, Juliana F

AU - Bosch, Soraya S

AU - Lunev, Sergey

AU - Wrenger, Carsten

AU - Groves, Matthew R

PY - 2020/2/1

Y1 - 2020/2/1

N2 - 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.

AB - 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.

KW - Protein oligomerisation

KW - malaria

KW - drug target validation

KW - phenotypic mapping

KW - FALCIPARUM DIHYDROOROTATE DEHYDROGENASE

KW - PLASMODIUM-VIVAX DHFR

KW - MALARIA PARASITES

KW - DRUG TARGET

KW - PIPERAQUINE RESISTANCE

KW - TRANSGENE EXPRESSION

KW - NEGATIVE SELECTION

KW - LEAD OPTIMIZATION

KW - GENE-EXPRESSION

KW - BLOOD STAGES

U2 - 10.1080/17460441.2020.1691996

DO - 10.1080/17460441.2020.1691996

M3 - Review article

VL - 15

SP - 189

EP - 202

JO - Expert Opinion on Drug Discovery

JF - Expert Opinion on Drug Discovery

SN - 1746-0441

IS - 2

ER -

ID: 112913137