In Silico Knockout Screening of Plasmodium falciparum Reactions and Prediction of Novel Essential Reactions by Analysing the Metabolic Network

Biomed Res Int. 2018 Mar 29:2018:8985718. doi: 10.1155/2018/8985718. eCollection 2018.

Abstract

Malaria is an infectious disease that affects close to half a million individuals every year and Plasmodium falciparum is a major cause of malaria. The treatment of this disease could be done effectively if the essential enzymes of this parasite are specifically targeted. Nevertheless, the development of the parasite in resisting existing drugs now makes discovering new drugs a core responsibility. In this study, a novel computational model that makes the prediction of new and validated antimalarial drug target cheaper, easier, and faster has been developed. We have identified new essential reactions as potential targets for drugs in the metabolic network of the parasite. Among the top seven (7) predicted essential reactions, four (4) have been previously identified in earlier studies with biological evidence and one (1) has been with computational evidence. The results from our study were compared with an extensive list of seventy-seven (77) essential reactions with biological evidence from a previous study. We present a list of thirty-one (31) potential candidates for drug targets in Plasmodium falciparum which includes twenty-four (24) new potential candidates for drug targets.

MeSH terms

  • Antimalarials / pharmacokinetics*
  • Antimalarials / therapeutic use
  • Drug Discovery / methods*
  • Humans
  • Malaria, Falciparum* / drug therapy
  • Malaria, Falciparum* / metabolism
  • Metabolome*
  • Models, Biological*
  • Plasmodium falciparum / metabolism*

Substances

  • Antimalarials