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dc.contributor.authorAltamura, Fernando-
dc.contributor.authorRajesh, Rishi-
dc.contributor.authorCatta-Preta, Carolina M. C.-
dc.contributor.authorMoretti, Nilmar Silvio [UNIFESP]-
dc.contributor.authorCestari, Igor-
dc.description.abstractHuman trypanosomiasis and leishmaniasis are vector-borne neglected tropical diseases caused by infection with the protozoan parasites Trypanosoma spp. and Leishmania spp., respectively. Once restricted to endemic areas, these diseases are now distributed worldwide due to human migration, climate change, and anthropogenic disturbance, causing significant health and economic burden globally. The current chemotherapy used to treat these diseases has limited efficacy, and drug resistance is spreading. Hence, new drugs are urgently needed. Phenotypic compound screenings have pre- vailed as the leading method to discover new drug candidates against these diseases. However, the publication of the complete genome sequences of multiple strains, advances in the application of CRISPR/Cas9 technology, and in vivo bioluminescence- based imaging have set the stage for advancing target-based drug discovery. This review analyses the limitations of the narrow pool of available drugs presently used for treating these diseases. It describes the current drug-based clinical trials highlighting the most promising leads. Furthermore, the review presents a focused discussion on the most important biological and pharmacological challenges that target-based drug discovery programs must overcome to advance drug candidates. Finally, it examines the advantages and limitations of modern research tools designed to identify and vali- date essential genes as drug targets, including genomic editing applications and in vivo imaging.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.publisherWilley Periodicalspt_BR
dc.relation.ispartofDrug Development Researchpt_BR
dc.rightsAcesso restritopt_BR
dc.subjectClinical trialpt_BR
dc.subjectCRISPR-Cas9 systemspt_BR
dc.subjectDrug discoverypt_BR
dc.subjectLeglected diseasespt_BR
dc.titleThe current drug discovery landscape for trypanosomiasis and leishmaniasis: challenges and strategies to identify drug targetspt_BR
dc.description.sponsorshipIDFAPESP: 2018/09948-0pt_BR
dc.identifier.doiDOI: 10.1002/ddr.21664pt_BR
unifesp.campusEscola Paulista de Medicina (EPM)pt_BR
unifesp.graduateProgramMicrobiologia e Imunologiapt_BR
unifesp.departamentoMicrobiologia, Imunologia e Parasitologiapt_BR
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