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In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni

2015-01Artigo científico Acesso aberto
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dc.contributor.authorNeves, Bruno J
dc.contributor.authorBraga, Rodolpho C
dc.contributor.authorBezerra, José C B
dc.contributor.authorCravo, Pedro V L
dc.contributor.authorAndrade, Carolina H
dc.contributor.institutionVector borne diseases and pathogens (VBD)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.pblPLOS - Public Library of Science
dc.date.accessioned2021-05-03T22:35:17Z
dc.date.available2021-05-03T22:35:17Z
dc.date.issued2015-01
dc.description.abstractMorbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent12
dc.format.extent1372012
dc.identifier.doi10.1371/journal.pntd.0003435
dc.identifier.issn1935-2727
dc.identifier.otherPURE: 3630945
dc.identifier.otherPURE UUID: 86d41967-4962-484e-9d0e-81d40c77db53
dc.identifier.otherPubMed: 25569258
dc.identifier.otherPubMedCentral: PMC4287566
dc.identifier.otherORCID: /0000-0003-1675-4504/work/71571117
dc.identifier.otherScopus: 84922256583
dc.identifier.urihttp://hdl.handle.net/10362/116837
dc.identifier.urlhttps://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003435
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAnimals
dc.subjectComputer Simulation
dc.subjectDrug Discovery
dc.subjectGenome, Helminth
dc.subjectGenomics
dc.subjectHelminth Proteins
dc.subjectLife Cycle Stages
dc.subjectSchistosoma mansoni
dc.subjectSchistosomiasis mansoni
dc.subjectSchistosomicides
dc.subjectJournal Article
dc.subjectResearch Support, Non-U.S. Gov't
dc.subjectDrug Discovery
dc.subjectParasitology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleIn silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansonien
dc.typejournal article
degois.publication.issue1
degois.publication.titlePLoS Neglected Tropical Diseases
degois.publication.volume9
dspace.entity.typePublication
rcaap.rightsopenAccess

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