Prioritising Flavonoids Reported in Moroccan Honeys against Influenza A Neuraminidase Structures using Docking Scores and Ligand Efficiency. 

Flavonoids found in honey have been studied for their potential antiviral activity. However, assessing these compounds against a single protein structure does not account for structural variability between targets. Also, it does not show if the compound rankings are consistent across the structures. This study compared the binding profiles of flavonoids reported in Moroccan honeys across multiple influenza A N1 and N2 neuraminidase structures. These flavonoids were studied as candidate complementary antivirals rather than replacements for existing neuraminidase inhibitors. 

Molecular docking of 31 flavonoids was performed against ten protein structures: three experimentally determined N1 structures, five experimentally determined N2 structures, and N1 and N2 models based on Moroccan influenza sequences. Oseltamivir, zanamivir and sialic acid were included as reference ligands. Compounds were prioritised primarily using docking scores (LeadFinder LF dG) and ligand efficiency (LF LE). Their physicochemical drug-likeness descriptors were also evaluated. 

Catechin gallate and epicatechin gallate ranked first or second on nine out of ten structures, with the most favourable docking score reaching -11.96 kcal/mol. Across the structures, reference ligands scored -6.9 to -9.7 kcal/mol (oseltamivir) and -8.7 to -11.7 kcal/mol (zanamivir). Both gallates received more favourable docking scores than oseltamivir on every structure and scores equal to or more favourable than zanamivir on most. Compound rankings showed strong agreement across the structures, including the Moroccan models (Kendall's W = 0.79, p < 10^-30). Gallocatechin ranked third on every structure but had the most favourable ligand efficiency in the series (-0.42 kcal/mol per heavy atom, comparable to zanamivir under the same protocol), with a molecular weight of 306 Da. 

These results support selecting gallocatechin and the gallated catechins for molecular dynamics simulations and experimental testing. The docking-score rankings were not dependent on any single protein structure. These predictions do not establish neuraminidase inhibition or antiviral activity.