Exploration of aminoacyl-tRNA synthetases from eukaryotic parasites for drug development |
| |
Authors: | Jasmita Gill Amit Sharma |
| |
Affiliation: | 1.ICMR-National Institute of Malaria Research, New Delhi, India;2.Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India;3.Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India |
| |
Abstract: | Parasitic diseases result in considerable human morbidity and mortality. The continuous emergence and spread of new drug-resistant parasite strains is an obstacle to controlling and eliminating many parasitic diseases. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous enzymes essential for protein synthesis. The design and development of diverse small molecule, drug-like inhibitors against parasite-encoded and expressed aaRSs have validated this enzyme family as druggable. In this work, we have compiled the progress to date towards establishing the druggability of aaRSs in terms of their biochemical characterization, validation as targets, inhibitor development, and structural interpretation from parasites responsible for malaria (Plasmodium), lymphatic filariasis (Brugia,Wuchereria bancrofti), giardiasis (Giardia), toxoplasmosis (Toxoplasma gondii), leishmaniasis (Leishmania), cryptosporidiosis (Cryptosporidium), and trypanosomiasis (Trypanosoma). This work thus provides a robust framework for the systematic dissection of aaRSs from these pathogens and will facilitate the cross-usage of potential inhibitors to jump-start anti-parasite drug development. |
| |
Keywords: | Plasmodium Brugia giardia Toxoplasma gondii leishmania Cryptosporidium trypanosoma aminoacyl-tRNA synthetases drug discovery |
|
|