While there has been no pandemic outbreak of influenza evolving from the H5N1 strain yet, the virus has already killed people. This suggests that without any significant mutations the influenza virus can live within the human body for days in which its life cycles can continue. The first step for infection is the host cell surface binding which is the function of the glycoprotein hemagglutinin (HA). In this investigation, quantum chemical calculations were performed on the systems comprising four structures coming from parts of the HA, with its cell receptor-analog substrate, determined from X-ray structures of the 1934 Spanish flu and avian influenza antigens. The calculations are aimed at partitioning the system into several parts, thus obtaining global and partial contributions of binding energy from each of them. As a result, it was possible to propose quantitatively the main contributions of key amino residues of the avian influenza virus glycoprotein around the binding pocket relevant to the binding process.The main binding energy contributions of the Spanish flu HA were from Tyr95, Val135, Thr136, Ala137, Glu190, Asp225, and Gln226, while the main contributions of the avian flu HA were from Ser129, Val131, Ser132, and Ser133. It was also found that the effect from the HA with an avian characteristic, Gln226 and Gly228, was not relatively high according to the contributed binding energy, whereas the effect from nearby water molecules was significant. Thus, it was concluded that both human and avian virus HA could recognize human cell receptors better than the avian cell receptors according to the binding energy. Therefore, the preference to any particular cell receptor types might involve some other factors rather than being determined solely by the HA binding process.
Structural Characterization of the 1918 Influenza Virus H1N1 Neuraminidase
