IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Open source Bioinformatics tools for the development of new TB drugs
Autor/es:
DEFELIPE, LUCAS; SOSA, EZEQUIEL J.; MARCELO MARTÍ; MODENUTTI, CARLOS; ADRIAN TURJANSKI; LEANDRO RADUSKY; DARÍO A. FERNÁNDEZ DO PORTO
Lugar:
Buenos Aires
Reunión:
Congreso; International Congress on Infectious Diseases (ICID); 2018
Resumen:
Background: In 2016 an estimated 6.3 million people developed tuberculosis (TB), and 1.8 million died from the disease. There is an urgent need for new anti-TB drugs owing to the following: the fact that current treatments have severe side effects, the increasing emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb), the negative drug-drug interactions with HIV (or another disease) treatments and the ineffectiveness of current drugs against dormant Mtb.Methods & Materials: In this context, we present two different tools to aid in the discovery of new anti TB drugs: the TuberQ database, a unique resource for all researchers working in the field of TB drug development provides a druggability analysis of all Mtb proteins consistently and efficiently, contributing to a better selection of potential drug targets for screening campaigns and the study of targets for structure-based drug design projects. Secondly, LigQ, a free web server that is able to: (i) determine best structure and ligand binding pocket for the desired protein, (ii) find known binders, as well as potential ligands known to bind to similar protein domains, (iii) most importantly, select a small set of commercial compounds enriched in potential binders, and (iv) prepare them for virtual screening.Results: Using both these tools we searched for new targets based on the hypotesis that ?if we know which proteins are targeted by RNOS and kill TB, we we might be able to inhibit them with drugs resulting in a synergistic bactericidal effect?. Based on this idea, we performed an Mtb metabolic network whole proteome analysis of potential RNOS sensitive and relevant targets which includes target druggability and essentiality criteria. Our results, available at http://tuberq.proteinq.com.aryield new potential TB targets, like I3PS, while also providing and updated view of previous proposals becoming an important tool for researchers looking for new ways of killing TB.