title: Inhibitors of RNA editing as potential chemotherapeutics against trypanosomatid pathogens.
abstract: The related trypanosomatid pathogens, Trypanosoma brucei spp., Trypanosoma cruzi and Leishmania spp. cause devastating diseases in humans and animals and continue to pose a major challenge in drug development. Mitochondrial RNA editing, catalyzed by multi-protein complexes known as editosomes, has provided an opportunity for development of efficient and specific chemotherapeutic targets against trypanosomatid pathogens. This review will discuss both methods for discovery of RNA editing inhibitors, as well as inhibitors against the T. brucei editosome that were recently discovered through creative virtual and high throughput screening methods. In addition, the use of these inhibitors as agents that can block or perturb one or more steps of the RNA editing process will be discussed. These inhibitors can potentially be used to study the dynamic processing and assembly of the editosome proteins. A thorough understanding of the mechanisms and specificities of these new inhibitors is needed in order to contribute to both the functional studies of an essential gene expression mechanism and to the possibility of future drug development against the trypanosomatid pathogens.
authors.affiliation: Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G1Y6 ; Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Quebec, Canada H9X3V9 ; McGill Centre for Bioinformatics, McGill University, Bellini Building, 3649 Promenade Sir William Osler, Montreal, Quebec, Canada H3G0B1.
authors.forename: Reza
authors.initials: R
authors.lastname: Salavati
authors.affiliation: Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G1Y6 ; Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Quebec, Canada H9X3V9.
authors.forename: Houtan
authors.initials: H
authors.lastname: Moshiri
authors.affiliation: Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Quebec, Canada H9X3V9.
authors.forename: Smriti
authors.initials: S
authors.lastname: Kala
authors.affiliation: Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Quebec, Canada H9X3V9 ; McGill Centre for Bioinformatics, McGill University, Bellini Building, 3649 Promenade Sir William Osler, Montreal, Quebec, Canada H3G0B1.
authors.forename: Hamed
authors.initials: H
authors.lastname: Shateri Najafabadi
keywords: High-throughput screening; RNA editing inhibitor; Trypanosomatids; Virtual screening