"Candidatus Liberibacter asiaticus" (Ca. L. asiaticus) is the causal agent of Huanglongbing disease of citrus and current study focuses on the discovery of novel small-molecule inhibitors against SecA protein of Ca. L. asiaticus. In this study, homologous modeling was used to construct the three-dimensional structure of SecA. Then, molecular docking-based virtual screening and two rounds of in vitro bacteriostatic experiments were utilized to identify novel small-molecule inhibitors of SecA. Encouragingly, 93 compounds were obtained and two of them (P684-2850, P684-3808) showed strong antimicrobial activities against Liberibacter crescens BT-1 in bacteriostatic experiments. Finally, molecular dynamics simulations were employed to explore the binding modes of the receptor-ligand complexes. Results in MD simulations showed that compound P684-3808 was relatively stable during simulation, while compound P684-2850 left the binding pocket. Compound P684-3808 might be suitable as a lead compound for further development of antimicrobial compounds against SecA of Ca. L. asiaticus.
Keywords: Candidatus Liberibacter asiaticus; SecA inhibitors; biological experiment; molecular dynamics simulations; virtual screening.
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