The development of new therapeutic leads against leishmaniasis relies primarily on screening of a large number of compounds on multiplication of clinically irrelevant transgenic promastigotes. The advent of the successful in vitro culture of axenic amastigotes allows the development of transgenic axenic amastigotes as a primary screen which can test compounds in a high throughput mode like promastigotes, still representative of the clinically relevant mammalian amastigotes stage. The present study reports the development of luciferase-tagged axenic amastigotes of Leishmania donovani, the causative agent of Indian Kala-azar, for in vitro drug screening. Luciferase expressing promastigotes were transformed to axenic amastigotes at a low pH and high temperature without the loss of luciferase expression. As compared to transgenic promastigotes, the luciferase expressing axenic amastigotes exhibited more sensitivity to antileishmanial drugs, particularly to pentavalent antimony (~2.8-fold) and also to the test compounds. Hence, the developed luciferase expressing axenic amastigotes make an ideal choice for high throughput drug screening for antileishmanial compounds.

Current treatment of leishmaniasis is based on chemotherapy, which relies on a handful of drugs with serious limitations, such as high cost, toxicity, and lack of efficacy in endemic regions. Therefore, development of new, effective, and affordable anti-leishmanial drugs is a global health priority. Dipeptidylcarboxypeptidase has been characterized and established as a drug target for antileishmanial drug discovery. We virtually screened a large chemical library of 15 452 compounds against a 3D model of dipeptidylcarboxypeptidase to identify novel inhibitors. The initial virtual screening using a ligand-based pharmacophore model identified 103 compounds. Forty-six compounds were shortlisted based on the docking scores and other scoring functions. Further, these compounds were subjected to biological assay, and four of them belonging to two chemical classes were identified as the lead compounds. Identification of these novel and chemically diverse inhibitors should provide leads to be optimized into candidates to treat these protozoan infections.

We present simulation results of the ground state structure and dynamics of quantum droplets in one-dimensional spin-orbit coupled binary Bose-Einstein condensates. We have considered two cases for this analysis, such as (i) the mean-field term has a vanishingly small contribution utilizing the equal and opposite inter- and intraspecies interaction and (ii) unequal inter- and intraspecies interaction. The quantum droplet exhibits remarkably different natures in each case. In the former case, it exhibits bright sech-like droplet nature, while in the latter case, we find the flattened sech-like shape of the droplet. Further, we analyze the effect of velocity perturbation on the dynamics in both cases. For the first case, we find a systematic change from the solitonic droplet nature to the breathing droplet which finally has a moving droplet feature upon increasing the velocity. However, the second case shows similar dynamics except having more dynamically stable features than the first. Finally, we present various dynamics that ensued in the quantum droplet due to the quenching of the interaction parameters, coupling parameters or allowing the droplet to undergo collisions.

Chemotherapy is the key intervention to control visceral leishmaniasis (VL), a neglected tropical disease. Current regimens include not only a few drugs but also present several drawbacks, including moderate to severe toxicity, cost, long-term administration, patient compliance, and growing drug resistance.