Background: 1.2-2.0 million cases of leishmaniasis occur annually throughout the world.
The available drugs like Amphotericin B, antimonials and miltefosine are unable to fulfill the need
due to less effectiveness, high toxicity, resistance, high cost and complex route of administration.
Leishmania survives inside the macrophages through different evasion mechanisms; one of that is
activation of its trypanothione reductase enzyme which neutralizes the reactive oxygen species generated
inside the macrophages to kill the parasites. This enzyme is unique and absent in human,
therefore in this study I targeted it for screening of new inhibitors to fight against leishmaniasis.
Methods: Homology modeling of Leishmania major trypanothione reductase was performed using
Phyre2 server. The homology based modelled protein was validated with PROCHECK analysis.
Ligplot analysis was performed to predict the active residues inside the binding pocket. Further, virtual
screening of ligand library containing 113 ligands from PubChem Bioassay was performed
against the target using AutoDock Vina Tool.
Results: Top five ligands showed best binding affinity. The molecule having PubChem CID:
10553746 showed highest binding affinity of -11.3 kcal/mol. Over all this molecule showed highest
binding affinity and moderate number of hydrogen bonds. Hopefully, this molecule will be able to
block the activity of target enzyme, trypanothione reductase of Leishmania major effectively and
may work as new molecules to fight against cutaneous leishmanaisis.
Conclusion: This study will help the researchers to identify the new molecules which can block the
activity of leishmanial-trypanothione reductase, a novel enzyme of trypanosomatids. These screened
inhibitors may also be effective not only in leishmaniasis but also other trypanosomatid-mediated