Influenza virus hemagglutinin spike neck architectures and interaction with model enzymes evaluated by MALDI-TOF mass spectrometry and bioinformatics tools

► Efficiency and specificity of influenza HA digestion by two model enzymes was assessed. ► Cleavage sites were found in the HA spike neck of enzyme-digested and control virions. ► Bromelain and subtilisin 3-D models were super-positioned to the HA spike. ► Intrinsic disorder predicted in HA membrane proximal region helps enzyme steric access. ► HA subtype/type specific architectures influence significantly the enzyme preferences.