IN SILICO EVALUATION OF NIGELLA SATIVA PHYTOCHEMICALS AS POTENTIAL INHIBITORS OF ODORANT-BINDING PROTEIN (PDB ID: 4KG2) OF ANOPHELES GAMBIAE.

Abstract Malaria, transmitted primarily by the Anopheles gambiae mosquito, remains a major public health burden in sub-Saharan Africa. The mosquito's highly efficient olfactory system, particularly the role of Odorant-Binding Proteins (OBPs) like OBP4 in detecting human hosts, presents a viable target for disrupting vector behavior. This study aimed to identify phytochemicals from Nigella sativa (Black Seed) as potential inhibitors of OBP4 (PDB ID: 4KG2) using in silico methods. The 3D structure of OBP4 was retrieved and prepared for docking. Phytochemicals from N. sativa were identified via GC-MS analysis, and their structures were optimized. Molecular docking was performed using AutoDock Vina to predict binding affinities and interaction modes. The top-scoring compounds were subsequently subjected to ADMET and toxicity profiling using SwissADME, ProTox-II, and DataWarrior. Docking results revealed that 9,12-Octadecadienoic acid (Z,Z)- (Linoleic acid) had the highest binding affinity (-8.59 kcal/mol), with other fatty acid esters also showing significant binding. The interactions were predominantly hydrophobic, consistent with OBP4's binding pocket characteristics. ADMET analysis indicated favorable drug-likeness and pharmacokinetic properties for most top binders. However, toxicity screening was crucial in identifying Linoleic acid as a safe lead candidate while disqualifying another strong binder, Diisooctyl phthalate, due to predicted mutagenicity. The study concludes that Linoleic acid and related esters from N. sativa are promising natural inhibitors of OBP4. These findings provide a molecular rationale for the documented repellent activity of Black Seed and highlight its potential as a source for developing eco-friendly malaria vector control agents. Further in vitro and in vivo validations are recommended.