IN SILICO ANTIMALARIAL TARGET SELECTION CONSERVED IN FOUR PLASMODIUM SPECIES

Oladoja AWofisayo

doi:10.22270/ujpr.v5i5.483

Oladoja AWofisayo Department of Pharmaceutical and Medicinal Chemistry, University of Uyo, Nigeria

10.22270/ujpr.v5i5.483

Keywords:

Antimalarial drugs, parasite, plasma DB, Plasmodium targets

Abstract

Objectives: The need for new antimalarials drugs and drug targets is pertinent due to the emergence of drug resistant strains of the parasites. Improper target selection has resulted in therapeutic failure. The genomic/post genomic era has made possible the deciphering of the 3D crystal structures of proteins and DNA which are drug targets and are deposited in the protein data bank.

Methods: Novel antimalarial targets obtained from evolutionary conserved short sequence motifs are utilised and are essential in transcription processes in the parasite. The motifs TGCATGCA, GTGCAC and GTGCGTGC were curated from experimental work, validated and analysed via phylogenomics genomics and comparative genomics. PlasmoDB blastn was applied to determine their similarity in Plasmodium vivax, knowlesi, Ovale and yoeli. The complete genome of Plasmodium falciparum vivax, knowlesi, Ovale and yoeli was downloaded from the plasmoDB and their positions determined.

Results: The targets are essential, conserved in rodent and mammalian species via phylogenomics with percentage identity and similarity greater than 80%, have no similar genes in the same genome and also found to be selective in the parasites vis-à-vis the Homo sapiens via comparative genomics with 0% identity and similarity in the human genome.

Conclusion: The targets reveal at the molecular and biochemical level, the vulnerable regions in the parasite while safe in human hence their choices in subsequent rationale drug discovery and design protocols.