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Computer‐Aided Discovery of Trypanosoma brucei RNA ‐Editing Terminal Uridylyl Transferase 2 Inhibitors
Author(s) -
Demir Özlem,
Labaied Mehdi,
Merritt Chris,
Stuart Ken,
Amaro Rommie E.
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12302
Subject(s) - trypanosoma brucei , virtual screening , drug discovery , trypanocidal agent , transferase , african trypanosomiasis , rna , computational biology , drug , biology , enzyme , biochemistry , chemistry , virology , pharmacology , trypanosomiasis , gene
Human African trypanosomiasis ( HAT ) is a major health problem in sub‐Saharan Africa caused by Trypanosoma brucei infection. Current HAT drugs are difficult to administer and not effective against all parasite species at different stages of the disease which indicates an unmet pharmaceutical need. Tb RET 2 is an indispensable enzyme for the parasite and is targeted here using a computational approach that combines molecular dynamics simulations and virtual screening. The compounds prioritized are then tested in T. brucei via Alamar blue cell viability assays. This work identified 20 drug‐like compounds which are candidates for further testing in the drug discovery process.