Open source Bioinformatics tools for the development of new TB drugs

RADUSKY, LEANDRO; FERNANDEZ DO PORTO, D.; DEFELIPE, LUCAS A.; SOSA, EZEQUIEL J.; TURJANSKI, ADRIÁN G.; MODENUTTI, CARLOS P.; MARTI, MARCELO A.

Buenos Aires

Congreso; ICID 2018; 2018

ISID

Background: In 2016 an estimated 6.3 million people developed tuberculosis (TB), and 1.8 million diedfrom the disease . There is an urgent need for new anti-TB drugs owing to the following: the fact thatcurrent treatments have severe side effects, the increasing emergence of multidrug-resistant strains ofMycobacterium 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 TBdrugs: the TuberQ database, a unique resource for all researchers working in the field of TB drugdevelopment provides a druggability analysis of all Mtb proteins consistently and efficiently, contributingto a better selection of potential drug targets for screening campaigns and the study of targets forstructure-based drug design projects. Secondly, LigQ, a free web server that is able to: (i) determine beststructure and ligand binding pocket for the desired protein, (ii) find known binders, as well as potentialligands known to bind to similar protein domains, (iii) most importantly, select a small set of commercialcompounds 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 knowwhich proteins are targeted by RNOS and kill TB, we we might be able to inhibit them with drugs resultingin a synergistic bactericidal effect?. Based on this idea, we performed an Mtb metabolic network wholeproteome analysis of potential RNOS sensitive and relevant targets which includes target druggability andessentiality 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 forresearchers looking for new ways of killing TB.Conclusion: Both TuberQ and LigQ are freely available at http://http://tuberq.proteinq.com.ar/ andhttp://ligq.qb.fcen.uba.ar/