In-Silico Identification of the Best Compound Against Leishmania infantum: High Throughput Screening of All FDA Approved Drugs
Journal Title: Turkish Journal of Parasitology - Year 2019, Vol 43, Issue 4
Abstract
Objective: Current in-silico research was designed and administered for the screening of 20000 Food and Drug Administration-approved drug compounds with the goal of finding promising drugs against lipophosphoglycan (LPG) and γ-glutamylcysteine synthetase (γ-GCS) of Leishmania infantum. Methods: After the protein sequence of both targets was taken, the 3D structures of protein of interest were predicted and validated. Molecular docking was done among the two putative targets (LPG and γ-GCS) and approved compounds were selected using AutoDock 4.2 program to predict ligand-receptor interactions. Results: After docking experiment was done on 20000 drug compounds, a total number of seven ligands, two for γ-GCS receptor and five for LPG receptor, were assigned as novel, potent anti-leishmanial drugs based on their binding affinity and energy. Of those, five ligands possessed cytotoxic and anti-cancer characteristics and showed good binding capacity to LPG receptor with ΔGbinding up to 8.5 kcal/mol more negative; while two compounds showed good binding capacity to glutamyl receptor with ΔGbinding up to 7.8 kcal/mol more negative. Conclusion: The latest software-based methods are powerful tools for scanning and predicting new peptide templates specific to biological targets in organisms for new drug discovery. However, the use of in vitro and in vivo techniques is a requirement for better evaluation of the potential of projected ligands with the help of in-silico approaches, identifying molecular mechanism of action of the more active compounds is possible. This can help in defining the most likely molecular target, so that the subsequent optimization using in vitro and in vivo techniques can be undertaken.
Authors and Affiliations
Jasem Saki, Farnoush Shadnoush, Reza Arjmand, Fakher Rahim
A Case of Rheumatoid Arthritis with Strongyloides stercoralis Hyperinfection
The patient was a 83-year- old male who worked as a farmer. He had complaints of weight loss, abdominal pain and joint pains for almost 5 months. Twenty days ago, the patient was checked at another hospital for complaint...
A Paediatric Case of Pulmonary Hydatid Cyst Presented with Mediastinal Lymphadenopathy
Hydatid cyst is a common zoonosis caused by larval forms of tapeworms called Echinococcus. The problem often occurs in the liver or lung. Cyst rupture and secondary bacterial infection are the most important complication...
Evaluation of Malaria Blood Smears Sent to National Malaria Reference Laboratory
Objective: Although the disease has been eliminated in Turkey malaria continues to be a threat due to increase in the number of people coming from or going to countries where the disease is endemic. In this study, we aim...
Visceral Leishmaniasis in A Patient Presenting with Fever of Unknown Origin: A Case Report From a Low-endemic Region of Turkey
Leishmaniasis is a neglected disease that is prevalent in tropical and subtropical regions of the world. Even though cutaneous leishmaniasis is the most common form, visceral leishmaniasis is associated with high mortali...
First Report of a Troglostrongylus brevior Case in a Domestic Cat in Turkey
Parasitic bronchopneumonia plays an important role, especially in the respiratory diseases of cats. Troglostrongylus species have been reported as lung parasites of wild cats; however, in recent years, they have also bee...