Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach

Abstract

Influenza infection poses a significant threat to the existence of humans and animals. Its inhibition by secondary metabolites may proffer a lasting solution to its resistance to available synthetic therapeutic agents. In this study, we investigated the influenza neuraminidase (NA) inhibitory potential of naturally occurring C–O–C biflavonoids using integrated computational approaches. The molecular docking method was employed to identify biflavonoids with high binding affinities, and molecular dynamics simulation was performed for 100 ns to examine the stability, binding mode, and interactions elicited by the hit molecules in influenza NA-binding pocket. The bioavailability and pharmacokinetic properties of the hit biflavonoids were examined using swissADME. The molecular docking studies identified lophirone L, delicaflavone, lanaroflavone, pulvinatabiflavone, and ochnaflavone as the hit molecules with the binding affinity of −9.9 to −9.3 kcal/mol. The root means square deviation and root mean square fluctuation plots obtained from the molecular dynamics simulation showed that the selected biflavonoids were reasonably stable at the enzyme’s binding pocket. The ADMET studies showed that the top-ranked biflavonoids exhibit good pharmacokinetic and bioavailability properties. Furthermore, the density functional theory studies showed that the selected hit secondary metabolite possesses good pharmacological properties. Thus, the inhibitory activities of these compounds on viral neuraminidase could be helpful in the management of influenza infections.

Keywords

• influenza
• influenza neuraminidase
• molecular docking
• molecular dynamics simulation
• bioavailability