In Silico Identification of Antimalarial Drug Targets and Screening of Potential Inhibitors in Plasmodium vivax

Abstract

Abstract
Malaria is an infectious disease caused by the protozoan of the genus Plasmodium. It is a major problem in third-world countries, with hundreds of millions of infections and millions of fatalities annually. Plasmodium vivax is the most frequent and widely distributed cause of recurring (Benign tertian) malaria. Due to emergence of drug-resistance, one has to explore new dimensions in order to curb the menace. We propose a two-step strategy—first step involves identification of potent drug targets of P. vivax using knowledge-based approaches, and in the next step Plasmepsin V is selected as a potent drug target for inhibitor identification. Plasmepsin V belongs to an aspartic protease family and exports the protein to host cell which is a crucial step in parasite survival. The conserved and variable regions are identified by using alignment algorithms. The available 3D structure of Plasmepsin V is energy minimized and validated. Active site was predicted by CASTp server. A “Similarity search” criterion is used for preparing in house lead database using DrugBank and PubChem databases. The gradient optimization method is used for screening the database. Some compounds showing high binding affinity than native inhibitors of Plasmepsin V. The identified drug compounds follow Lipinski’s rule of five and have the desired ADMET properties. In light of physicochemical properties, these identified inhibitors should be treated only as drug prototypes for antimalarial drugs.

Keywords: Plasmepsin V, drug target, proteases, drug design, virtual screening, active site, physicochemical properties, Structure validation

Cite this Article
Nimita
Sharma, Manoj Kumar Yadav In
Silico Identification of Antimalarial Drug
Targets and Screening of Potential
Inhi bitors in Plasmodium vivax Research
& Reviews: Journal of Computational
Biology. 2020; 9(1): 52 75 p.