A systematic in silico search for target similarity identifies several approved drugs with potential activity against the Plasmodium falciparum apicoplast

PLoS One. 2013;8(3):e59288. doi: 10.1371/journal.pone.0059288. Epub 2013 Mar 26.


Most of the drugs in use against Plasmodium falciparum share similar modes of action and, consequently, there is a need to identify alternative potential drug targets. Here, we focus on the apicoplast, a malarial plastid-like organelle of algal source which evolved through secondary endosymbiosis. We undertake a systematic in silico target-based identification approach for detecting drugs already approved for clinical use in humans that may be able to interfere with the P. falciparum apicoplast. The P. falciparum genome database GeneDB was used to compile a list of ≈600 proteins containing apicoplast signal peptides. Each of these proteins was treated as a potential drug target and its predicted sequence was used to interrogate three different freely available databases (Therapeutic Target Database, DrugBank and STITCH3.1) that provide synoptic data on drugs and their primary or putative drug targets. We were able to identify several drugs that are expected to interact with forty-seven (47) peptides predicted to be involved in the biology of the P. falciparum apicoplast. Fifteen (15) of these putative targets are predicted to have affinity to drugs that are already approved for clinical use but have never been evaluated against malaria parasites. We suggest that some of these drugs should be experimentally tested and/or serve as leads for engineering new antimalarials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemistry*
  • Antimalarials / pharmacology
  • Computer Simulation
  • Databases, Genetic
  • Databases, Pharmaceutical
  • Drug Design
  • Gene Expression Regulation
  • Models, Chemical*
  • Molecular Targeted Therapy*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism
  • Plastids / drug effects*
  • Plastids / genetics
  • Plastids / metabolism
  • Protein Sorting Signals / genetics
  • Protozoan Proteins / antagonists & inhibitors
  • Protozoan Proteins / chemistry*


  • Antimalarials
  • Protein Sorting Signals
  • Protozoan Proteins

Grant support

This work was funded by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/PVE of Brazil (http://www.capes.gov.br/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.