Moderate DNA and high SARS-CoV-2 spike protein affinity of oxidovanadium(IV) complexes of 2-furoic acid hydrazones: In silico and in vitro approach

Abstract

The interaction of five neutral heteroleptic octahedral paramagnetic mononuclear oxidovanadium(IV) complexes of general composition [VIVO(bpy)L], where L is a dianionic tridentate ONO-donor hydrazone ligand derived from 2-furoic acid hydrazide and salicylaldehyde and its 5-substituted derivatives with spike protein SARS-CoV-2 was investigated in silico and in vitro. Molecular docking indicates that the complexes have high affinity for SARS-CoV-2 spike protein binding, and that the complex with a nitro substituent on the salicylaldehyde component of the hydrazone ligand has the highest binding potential. The interaction of this complex was examined by spectrofluorimetry utilizing spectrofluorimetric titration, thermodynamic measurements and FRET analysis. The results suggest van der Walls forces and hydrogen bonding as the dominant modes of interaction of the complex with the SARS-CoV-2 spike protein, which is in agreement with theoretical predictions. Molecular docking was further employed to investigate the interaction of vanadium complexes with SARS-CoV-2 omicron variant (BA.1) RBD with human ACE2 protein. The interaction of the complex with CT DNA was investigated using electron spectroscopy and thermodynamic considerations. The complexes showed a moderate affinity for DNA as groove binders. The groove binding was confirmed by molecular docking with B-DNA. Also, druglikness properties of complexes were assessed by SwissADME. The strong antioxidant activity of the complexes, comparable to ascorbic acid, was evaluated by the DPPH method. This is the first experimental research that supports the thesis of molecular docking that vanadium compounds could be druggable against SARS-CoV-2 virus proteins.