Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets

PLoS One. 2017 Oct 31;12(10):e0186364. doi: 10.1371/journal.pone.0186364. eCollection 2017.


Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drugs to have been previously tested against malaria, with most showing activity. For further validation, drug susceptibility assays using SYBR Green I method were done on a representative group of 10 predicted drugs, eight of which did show activity against P. falciparum 3D7 clone. Seven had IC50 values ranging from 1 μM to 50 μM. This study also suggests drug-target association and hence possible mechanisms of action of drugs that did show antiplasmodial activity. The study results validate the use of proteome-wide target similarity approach in identifying approved drugs with activity against P. falciparum and could be adapted for other pathogens.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimalarials / pharmacology*
  • Antimalarials / therapeutic use
  • Databases, Factual
  • Drug Approval
  • In Vitro Techniques
  • Malaria, Falciparum / drug therapy*
  • Plasmodium falciparum / metabolism*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / metabolism*
  • Sequence Homology, Amino Acid


  • Antimalarials
  • Protozoan Proteins

Grant support

This work was supported by the Japan International Cooperation Agency (AFRICA-ai-JAPAN Research Fund), grant no; JKU/ADM/10B, (url: The grant number for financial support I received from JICA to facilitate part of this study is iCMOB/05/16 to RMM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.