Despite a century of control and eradication campaigns, malaria remains one of the world's most devastating diseases. Our once-powerful therapeutic weapons are losing the war against the Plasmodium parasite, whose ability to rapidly develop and spread drug resistance hamper past and present malaria-control efforts. Finding new and effective treatments for malaria is now a top global health priority, fuelling an increase in funding and promoting open-source collaborations between researchers and pharmaceutical consortia around the world. The result of this is rapid advances in drug discovery approaches and technologies, with three major methods for antimalarial drug development emerging: (i) chemistry-based, (ii) target-based, and (iii) cell-based. Common to all three of these approaches is the unique ability of structural biology to inform and accelerate drug development. Where possible, SBDD (structure-based drug discovery) is a foundation for antimalarial drug development programmes, and has been invaluable to the development of a number of current pre-clinical and clinical candidates. However, as we expand our understanding of the malarial life cycle and mechanisms of resistance development, SBDD as a field must continue to evolve in order to develop compounds that adhere to the ideal characteristics for novel antimalarial therapeutics and to avoid high attrition rates pre- and post-clinic. In the present review, we aim to examine the contribution that SBDD has made to current antimalarial drug development efforts, covering hit discovery to lead optimization and prevention of parasite resistance. Finally, the potential for structural biology, particularly high-throughput structural genomics programmes, to identify future targets for drug discovery are discussed.
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August 2014
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Review Article|
July 10 2014
From crystal to compound: structure-based antimalarial drug discovery
Nyssa Drinkwater;
Nyssa Drinkwater
*Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, VIC 3800, Australia
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Sheena McGowan
Sheena McGowan
1
*Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, VIC 3800, Australia
1To whom correspondence should be addressed (email Sheena.mcgowan@monash.edu).
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Publisher: Portland Press Ltd
Received:
February 19 2014
Revision Received:
April 17 2014
Accepted:
April 23 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 461 (3): 349–369.
Article history
Received:
February 19 2014
Revision Received:
April 17 2014
Accepted:
April 23 2014
Citation
Nyssa Drinkwater, Sheena McGowan; From crystal to compound: structure-based antimalarial drug discovery. Biochem J 1 August 2014; 461 (3): 349–369. doi: https://doi.org/10.1042/BJ20140240
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