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Researchers Publish Findings on Potential New Treatments for Leishmaniasis
By: Dr. Carlos Muskus López
Coordinator, Molecular Biology and Computational Unit, PECET University of Antioquia
8 Sep 2016   

Summary
The Drug Search for Leishmaniasis team recently published their findings in the Journal of Computer-Aided Molecular Design. Using World Community Grid's computing power, they have identified several drug compounds which may lead to improved treatments for this neglected and sometimes deadly disease.

One of the best ligands bound to the dihydrorootate dehydrogenase (DHODH) from Leishmania major. (a) Predicted binding within the crystal structure (b) Superimposition of the ligand conformations predicted to bind to each of the DHODH protein conformations extracted from the MD simulation

Background

Leishmaniasis, one of the most neglected tropical diseases in the world, infects more than two million people every year. The disease is caused by a parasite (genus Leishmania) which is transmitted between humans and animals by female sand flies. The number of cases continues to increase in tropical countries such as Bangladesh, India, Sudan, Ethiopia, Brazil, Colombia, Peru and others.

The existing treatments for leishmaniasis can cause severe side effects. Additionally, drug-resistant parasites are causing major problems in many countries. For these reasons, there is an urgent need for new, safe and inexpensive anti-leishmaniasis drug compounds.

Overview

In our paper, we describe the detailed steps we took to identify protein drug targets, which included the screening of 600,000 molecules to determine which might lead to development of new treatments for the disease. Specifically, we searched for drugs which target the proteins which are essential for the survival of the parasite that causes leishmaniasis. By finding molecules that bind to these proteins, they can potentially be disabled, thus stopping the infection and curing the disease.

The paper describes how some of the protein targets can bend and change shape, which presents some challenges in finding good candidate molecules. We discuss our approach to dealing with these problems.

Using the results computed on World Community Grid, we selected the ten best drug candidates for test-tube experiments, which yielded very promising results. In particular, one of the compounds appears to be able to kill the leishmaniasis parasite without affecting human cells in vitro. Three additional compounds also showed promising results.

We now plan to work to modify the three promising identified drug compounds to improve their potency, solubility and to minimize toxicity. We will also evaluate other top candidates depending on the funds we can raise. Furthermore, we are developing an open data platform with World Community Grid´s results so that other researchers can mine our data to detect additional drug hits or leads.

You can read an abstract of the paper here. We are grateful to all the World Community Grid volunteers who made this research possible by donating their computing power to this project.



 


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Project Update , Research Paper

Dr. Carlos Muskus López
Coordinator, Molecular Biology and Computational Unit, PECET University of Antioquia