Discovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design

Candidatus Liberibacter asiaticus is the causal agent of Huanglongbing (HLB) disease of citrus. Current management practices have not been able to control HLB and stop the spread of HLB. The current study is focused on screening small molecule inhibitors against SecA protein of Ca. L. asiaticus. Homology modeling, structure based virtual screening and molecular docking methods have been used to find the novel inhibitory compounds against SecA activity at ATP binding region. At 20 mu m 17 compounds showed >50% inhibition and four compounds had more than 65% inhibition. The most active compound has IC(50) value of 2.5 mu M. The differences between the activities of the compounds are explained by their inter-molecular interactions at ATP binding site. (C) 2011 Elsevier Ltd. All rights reserved.