In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni
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2015
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Morbidity 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.
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EVES, Bruno J. In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni. Plos Neglected Tropical Diseases, San Francisco, v. 9, n. 1, p. e3435, 2015.