Drug repurposing: mining protozoan proteomes for targets of known bioactive compounds.
J Am Med Inform Assoc
; 21(2): 238-44, 2014.
Article
en En
| MEDLINE
| ID: mdl-23757409
ABSTRACT
OBJECTIVE:
To identify potential opportunities for drug repurposing by developing an automated approach to pre-screen the predicted proteomes of any organism against databases of known drug targets using only freely available resources. MATERIALS ANDMETHODS:
We employed a combination of Ruby scripts that leverage data from the DrugBank and ChEMBL databases, MySQL, and BLAST to predict potential drugs and their targets from 13 published genomes. Results from a previous cell-based screen to identify inhibitors of Cryptosporidium parvum growth were used to validate our in-silico prediction method.RESULTS:
In-vitro validation of these results, using a cell-based C parvum growth assay, showed that the predicted inhibitors were significantly more likely than expected by chance to have confirmed activity, with 8.9-15.6% of predicted inhibitors confirmed depending on the drug target database used. This method was then used to predict inhibitors for the following 13 disease-causing protozoan parasites, including C parvum, Entamoeba histolytica, Giardia intestinalis, Leishmania braziliensis, Leishmania donovani, Leishmania major, Naegleria gruberi (in proxy of Naegleria fowleri), Plasmodium falciparum, Plasmodium vivax, Toxoplasma gondii, Trichomonas vaginalis, Trypanosoma brucei and Trypanosoma cruzi.CONCLUSIONS:
Although proteome-wide screens for drug targets have disadvantages, in-silico methods can be developed that are fast, broad, inexpensive, and effective. In-vitro validation of our results for C parvum indicate that the method presented here can be used to construct a library for more directed small molecule screening, or pipelined into structural modeling and docking programs to facilitate target-based drug development.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_chagas_disease
/
3_zoonosis
Asunto principal:
Parásitos
/
Simulación por Computador
/
Proteoma
/
Pruebas de Sensibilidad Parasitaria
/
Reposicionamiento de Medicamentos
/
Antiparasitarios
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Am Med Inform Assoc
Asunto de la revista:
INFORMATICA MEDICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos