Título :	Ferramentas virtuais contra doenças tropicais : dengue e doença de chagas como alvos Ferramentas virtuais contra doenças tropicais : dengue e doença de chagas como alvos
Autor :	Silva, Hugo de Almeida
Orientador(es)::	Santana, Jaime Martins de
Coorientador(es)::	Ribeiro, Bergmann Morais Maigret, Bernard
Assunto::	Doenças transmissíveis Dengue Chagas, Doença de Biotecnologia farmacêutica
Fecha de publicación :	7-feb-2013
Data de defesa::	2012
Citación :	SILVA, Hugo de Almeida. Ferramentas virtuais contra doenças tropicais: dengue e doença de chagas como alvos. 2012. 176 f., il. Tese (Doutorado em Patologia Molecular)—Universidade de Brasília, Brasília, 2012.
Abstract:	Despite affecting about one-sixt of the world's population, diseases like dengue fever and Chagas disease are still overlooked by the government and pharmaceutical industries. By assuming the responsibility over basic research, public institutions of higher education may play a role in making the development of new drugs against neglected diseases more attractive to the big pharma companies. With the aim of cutting costs and time for searching new drugs against those diseases, this work intended to apply in silico analysis methods towards the implementation of a rational drug design platform against neglected diseases occurring in Brazil. Thus, two illnesses for which there are no vaccines or effective treatments were chosen for a pilot study: dengue fever and Chagas disease. One of the most promising targets against dengue fever is the viral NS3 protease, which, together with its cofactor NS2B. promotes the viral polyprotein processing and therefore viral replication. By using comparative modeling techniques, molecular dynamics simulations and virtual screening, a possible role of the NS2B cofactor and the ligand binding in the induced fit effect at the NS3 active site was proposed. Also, four conformational families were found and explored in a virtual screening campaign, in which four compounds with proven inhibitory activity were found. At the same time, similar techniques were applied to two targets of Trypanosoma cruzi already studied by our team: the cathepsin B (TcCatB) and the methyltioadenosine phosphorilase (TcMTAP). The built models were shown to be stable during molecular dynamics simulations, and were also subjected to virtual screening campaigns. Molecules with putative inhibitory activity against those targets were detected. Together, those results point to the viability in establishing a rational drug discovery platform against neglected diseases.
metadata.dc.description.unidade:	Faculdade de Medicina (FM)
Descripción :	Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, Pós-Graduação em Patologia Molecular, 2012.
metadata.dc.description.ppg:	Programa de Pós-Graduação em Patologia Molecular
Aparece en las colecciones:	Teses, dissertações e produtos pós-doutorado

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