Identificação de potenciais inibidores bioativos para candidatus liberibacter asiaticus: uma abordagem computacional contra o agente causador do Huanglongbing (HLB)

Abstract

Huanglongbing (HLB), or greening, is one of the most severe diseases affecting global citriculture, primarily caused by the bacterium Candidatus Liberibacter asiaticus, a phloem-restricted phytopathogen transmitted by the insect vector Diaphorina citri. The urgency to find a solution lies in the severe economic and social impact of the disease in Brazil, one of the world's largest producers of Citrus spp. The specific inhibition of ABC family amino acid transporters, such as the cystine-binding subunit (TcyA)— essential for the microorganism's survival and antioxidant defense—represents a crucial management strategy. Therefore, this study aimed to identify potential bioactive inhibitors for this receptor using computational chemistry methodologies. The workflow involved high-throughput virtual screening, pharmacophore modeling, molecular docking, and molecular dynamics simulations (100 ns). The results culminated in the identification of the semisynthetic molecule NB_2472 as the lead candidate, demonstrating excellent thermodynamic affinity and restriction of the active site's conformational flexibility, combined with a highly favorable ADMET profile (absence of mutagenicity, industrial synthesis viability, and systemic translocation potential). Additionally, the compounds NB_2458 and NB_2471 stood out as promising strategic alternatives, prioritizing maximum toxicological safety and low synthesis cost, respectively. In conclusion, the applied in silico approach is indispensable for combating this unculturable phytopathogen, providing validated and safe molecular prototypes for the advancement of biotechnological investigations and in vitro tests.