Inhibition of influenza hemagglutinin with the antiviral inhibitor arbidol using a proteomics based approach and mass spectrometry

•In vitro, molecular experimental and computational study of the inhibition of influenza H1 hemagglutinin with arbidol.•Identification of arbidol contact residues in HA2 subunit by mass spectrometry.•Parallel molecular docking of arbidol to influenza H1 hemagglutinin.

A proteomics gel electrophoresis based approach has been applied to study the effect of arbidol on the proliferation of influenza virus in vitro through quantitation of hemagglutinin levels. An arbidol concentration of 20 μg/ml was required to achieve a 50% reduction in virus proliferation and hemagglutinin levels. The use of a MALDI mass spectrometry approach to study the binding of arbidol to influenza hemagglutinin revealed it bound solely to residues 104-120 of the HA2 subunit, a region known to contain an arbidol resistance mutation. Parallel molecular docking results revealed that this binding site was favoured in which the arbidol molecule binds in two possible orientations approximately 180° to one another at HA2 residues 118-123. The combined studies support the recognized potential of arbidol as an effective and targeted antiviral agent against the influenza virus.