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4.
PLoS One ; 7(7): e39808, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22808064

RESUMEN

A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative 'Connect to Decode' (C2D) to generate the first and largest manually curated interactome of Mtb termed 'interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.


Asunto(s)
Proteínas Bacterianas/metabolismo , Colaboración de las Masas , Sistemas de Liberación de Medicamentos/métodos , Genoma Bacteriano , Macrófagos/microbiología , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Proteínas Bacterianas/genética , Sistemas de Liberación de Medicamentos/estadística & datos numéricos , Redes Reguladoras de Genes , Genómica , Interacciones Huésped-Patógeno , Humanos , Mycobacterium tuberculosis/patogenicidad , Mapeo de Interacción de Proteínas , Proteoma , Transducción de Señal
5.
Tuberculosis (Edinb) ; 91(5): 479-86, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21782516

RESUMEN

It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery.


Asunto(s)
Antituberculosos , Factores Inmunológicos , Mycobacterium tuberculosis/patogenicidad , Apoyo a la Investigación como Asunto , Vacunas contra la Tuberculosis , Tuberculosis/prevención & control , Antituberculosos/uso terapéutico , Conducta Cooperativa , Diseño de Fármacos , Humanos , Factores Inmunológicos/uso terapéutico , India/epidemiología , Vacunas contra la Tuberculosis/economía
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