Drug target identification in protozoan parasites

ABSTRACT

Introduction: Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications.

Areas covered: Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail.

Expert opinion: Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.

KEYWORDS:

• Apicomplexa
• drug design
• kinetoplastida
• mode of action
• repurposing
• target

Article highlights

• Only a limited panel of drugs against protozoal parasites is on the market.

• These drugs were discovered by empirical studies on fundamental aspects of parasite biology, or by whole organism screening approaches.

• Many of these drugs target cellular processes such as replication, transcription, translation, respiration, and are therefore prone to side effects.

• By focusing on proteins that are specifically encoded by protozoan parasites, target based drug design aims to provide compounds with good efficacy and large therapeutical indexes.

• Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches should not yet be disregarded.

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Declaration of interest

The authors are supported by a National Institutes of Health/US Department of Agriculture grant R01HD080670, a Swiss National Science Foundation grant 310030_165782 and a Swiss State Secretariat for Education and Science grant C15.0034. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.