Drug Repurposing for Inhibiting Triose Phosphate Isomerase of Giardia lamblia (GlTIM) Using a Computational Approach

Adnan Shehzad; Fazal Rabi; Neelofar Shah; Muhammad Asif; Mohammad Latif; Noreen Begum; Bibi Ayesha; Hamid Ur Rahman

doi:10.70749/ijbr.v3i2.830

Authors

Adnan Shehzad Department of Biotechnology, COMSATS, Abbottabad, KP, Pakistan.
Fazal Rabi Centre for Animal Sciences & Fisheries, University of Swat, KP, Pakistan.
Neelofar Shah Atta-ur-Rehman School of Applied Biosciences, National University of Sciences and Technology (NUST), Islamabad, Pakistan.
Muhammad Asif Department of Zoology, Hazara University, Mansehra, KP, Pakistan.
Mohammad Latif Centre for Biotechnology and Microbiology, University of Swat, KP, Pakistan.
Noreen Begum Department of Zoology, Hazara University, Mansehra, KP, Pakistan.
Bibi Ayesha Department of Microbiology, Hazara University, Mansehra, KP, Pakistan.
Hamid Ur Rahman Department of Zoology, Hazara University, Mansehra, KP, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v3i2.830

Keywords:

Drug Repurposing, Giardiasis, GlTIM

Abstract

Background: Giardiasis is caused by an intestinal flagellated protozoan parasite, Giardia lamblia. This pathogen can infect many hosts, including domestic and wild animals and humans. It is responsible for 280 million symptomatic individuals worldwide, with a prevalence of 2 to 5% in industrialized countries and 20 to 30% in developing countries. Few antiprotozoal drugs are used to cure giardiasis; albeit with the resistance shown by the parasite to many of these drugs. Alternative drugs are continuously needed to be developed. One of the key proteins to target is Giardia lamblia Triose phosphate Isomerase (GlTIM), an enzyme involved in glycolysis as well as gluconeogenesis. Objective: The present study was designed to find inhibitors for GlTIM through an insilico approach, utilizing drugs that are already in use for other diseases. Methods: The GlTIM 3D structure was obtained from the protein database. From ChemSpider, one hundred and forty potential drugs, already approved by the FDA, were retrieved and docked utilizing the PatchDock server, results with the highest interactions were selected. The GS viewer and LIGPLOT+ were used to visualize the interactions, which included hydrogen bonding, covalent and hydrophobic interactions. Results: Interactions with the target active site residues suggest the possible inhibition that these ligands can potentiate. The drugs with the highest interaction in the current study include Daptomycin, Vancomycin and Cefazedone. Conclusions: The inhibition of GlTIM by these drugs demonstrates that drug repurposing is an important pharmaceutical strategy that can yield new therapeutics in less time and fewer resources for this parasitic disease.

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