Submit Manuscript  

Article Details


Apicoplast Import Protein Tic20 A Promising Therapeutic Molecular Target for Plasmodium falciparum: An In Silico Approach for Therapeutic Intervention

[ Vol. 17 , Issue. 3 ]

Author(s):

Ravi C P. K. Srimath-Tirumala-Peddinti, Sandeep S. Kusuma, Deepthi Nammi and Nageswara R.R. Neelapu*   Pages 199 - 222 ( 24 )

Abstract:


Background: Malaria is a lethal disease causing mortality to over millions each year. Drug resistance in the malarial parasite spurred effects to discover effective antimalarial drug targets and drugs. An objective of this current study is to identify drug targets for malarial parasite. Genes unique, non-homologous to humans and essential for parasite are identified using BLASTn by comparing genomes between parasite and host.

Objective: Further open BLASTp was used to filter the targets specific to Plasmodium species and later were subjected to gene property analysis to identify 65 potential targets. Screening of potential drug targets for the drug target properties like virulence and enzyme identified three drug targets with virulence property and eleven with enzymatic nature.

Method: Thirteen knockouts related to potential drug targets were already tested in Plasmodium species, non-Plasmodium species and rodent malaria, lending credence to our approach. 3-D structures of 27 drug targets were predicted using I-tasser server and apicoplast import protein Tic20 is the best modeled protein. Gene ontology studies and analysis for motifs on nuclear localization signal (NLS) established apicoplast import protein Tic20 as an import protein. In silico docking studies were used to establish the druggability of apicoplast import protein Tic20.

Result and Conclusion: In silico docking studies on 3-D structure generated using I-tasser with quinine, chloroquine, artesunate into the active site of apicoplast import protein Tic20 established apicoplast import protein Tic20 as a promising therapeutic molecular target.

Keywords:

Drug targets, in silico docking, host – pathogen comparison, 3-D structure modeling, malaria.

Affiliation:

Department of Bioinformatics, School of Life Sciences, GITAM Institute of Science, GITAM University, Rushikonda campus, Visakhapatnam – 530045 (AP), Department of Bioinformatics, School of Life Sciences, GITAM Institute of Science, GITAM University, Rushikonda campus, Visakhapatnam – 530045 (AP), Department of Bioinformatics, School of Life Sciences, GITAM Institute of Science, GITAM University, Rushikonda campus, Visakhapatnam – 530045 (AP), Department of Bioinformatics, School of Life Sciences, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam- 530045. AP

Graphical Abstract:



Read Full-Text article