A Computational Molecular Docking Studies on the Tryparedoxin Peroxidase of Leishmania donovani Responsible for Visceral Leishmaniasis in Human

Background: Visceral leishmaniasis, the most lethal form of Leishmaniasis, is caused by Leishmania donovani in the Indian subcontinent and East Africa. Current therapeutics for the disease is associated with a risk of high toxicity and development of drug-resistant strains. Thus, the discovery of potential targets, successful inhibitors, and improved drug distribution mechanisms for leishmaniasis diagnosis has become a focus. Objective: Hydroperoxide metabolism involving trypanothione, key for the survival of Leishmania, is a validated target for rational drug design. In this study, we aim in silico drug design by targeting tryparedoxin peroxidase (2-Cysperoxiredoxin type) from Leishmania donovani (LdTXNPx) using clioquinol, nelfinavir, and strychnobiflavone as mother compound. Clioquinol, nelfinavir are known for their anti-leishmanial activity and strychnobiflavone showed antileishmanial activity against Leishmania amazonensis and Leishmania infantum amastigotes and promastigotes recently. Methods: On this basis, we constructed protein structure using homology modeling, molecular docking of protein with potential drug candidates, interaction analysis and pharmacophore analysis conducted in this study. Results: We have revealed two compounds i.e. Nelfinavir mesylate and strychnobiflavone, which have desired characteristics in the future drugs for Visceral leishmaniasis. Conclusion: Consistently in the future, we will ratify the efficacy of these compounds, essential animal and clinical trials are needed to be performed. We believe that our present study will help to find efficient and effective therapy for treating Visceral leishmaniasis in humans.