Cysteine Proteases as Malarial Drug Targets
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Cysteine Proteases as Malarial Drug Targets

This work was part of the projects of three research students; Aquillah Kanzi, Matthys Kroon, Joyce Njuguna.

Malaria is a devastating infectious parasitic disease with mortality rates of more than a million annually. It is caused by parasites of the Plasmodium species. Treatment of malaria is limited by parasite resistance to available drugs. Hence, there is continuous need for identification of new drug targets and anti-malarial compounds. This work focused on a group of Plasmodium falciparum cysteine proteases, falcipains, that belong to the clan CA and papain family C1. The study is divided into three parts:

  1. Characterization of the prodomain’s regulatory effect in falcipain-2, a validated drug target, and its homologs in other Plasmodium species with an attempt to design short peptides as potential peptidomimetic therapeutic agents.
  2. Structural analysis of catalytic domain of falcipain homologs and molecular docking studies against South African natural compounds.
  3. Establishment of an alternative approach to protein-protein docking to study the interactions between cysteine proteases and their protein inhibitors on a large scale.


  1. Tastan Bishop, Ö. and Kroon, M. “Study of protein complexes via homology modeling, applied to cysteine proteases and their protein inhibitors” Journal of Molecular Modeling 17(12):3163-72, 2011.
  2. Njuguna, Joyce Njoki (2012) Structural Analysis of Prodomain Inhibition of Cysteine Proteases in Plasmodium species. Masters thesis, Rhodes University.
  3. Kanzi, Aquillah M (2013) Falcipains as Malarial Drug Targets. Masters thesis, Rhodes University (Under review – unpublished).
  4. Kroon, Matthys (2012) High-throughput modelling and structural investigation of cysteine protease complexes with protein inhibitors, Masters thesis, Rhodes University.