The former was developed earlier and most influenza viruses presently circulating among humans are resistant against the inhibitors from this group. These drugs were the only available options during the 2009 pandemic. Influenza type A and B viruses contain three major surface proteins, HA, NA and M2. HA mediates viral attachment to host cells by binding sialic acids on carbohydrate side chains of cell surface glycoproteins and glycolipids. HA also mediates virus entry into host cells through the fusion of the viral envelope with the 
endosomal membrane. As fusion occurs, the viral genome is released into cytoplasm of host cells by the aid of the M2 protein ion channel. NA cleaves the terminal sialic acid residues on oligosaccharide chains that serve as viral HA receptors. Through this enzymatic activity, NA plays an important role in the spread of infection from cell to cell because virions stick to the cell surface or aggregate with each other if sialic acid residues are not removed from the surface of infected cells and progeny viruses. In body fluids, numerous molecules containing sialic acid exist and most of them are able to bind to virus HA and inhibit the hemagglutination activity of influenza virus. Human saliva has been reported to contain such hemagglutination inhibitors. During the initial infection of mucosal epithelial cells, influenza virus encounters these inhibitory molecules in mucus and viral NA is speculated to inactivate such inhibitors so that viral HA is able to bind to receptors on the surface of epithelial cells. Influenza virus initiates infection in the upper respiratory tract where commensal bacterial flora exists. The synergism between influenza virus and bacteria has been documented in past influenza outbreaks. It was first observed when the swine influenza virus was discovered by Shope in 1931. He indicated that the isolated virus and Haemophilus influenzae acted together to produce swine influenza and that neither alone was capable of inducing disease. Furthermore, reexamination of samples from the influenza MG132 Proteasome inhibitor pandemic of 1918 indicated that the majority of Nilotinib abmole patients died of secondary bacterial pneumonia. In the influenza pandemic of 1957-1958, most deaths attributed to influenza A virus infection occurred concurrently with bacterial pneumonia. Moreover, recent postmortem studies among fatal Apdm09 cases from the 2009 pandemic established a link between bacterial lung infections and increased mortality or developing complications. Mechanisms for the synergy between bacteria and influenza viruses involve the activity of either bacterial or viral enzymes. For influenza virus to obtain membrane fusion activity, HA protein has to be cleaved by a host proteinase. Some strains of Staphylococcus aureus secrete a protease which significantly influences the outcome of influenza infection by cleavage activation of HA. Influenza virus NA, on the other hand, potentiates the development of pneumonia by stripping sialic acid from lung cells, thus exposing receptors for Streptococcus pneumoniae adhesion. Classical studies on influenza virus receptors by Gottschalk showed that neuraminidase treatment inactivates hemagglutination inhibitors in serum and mucus secretions by removing the sialic acid residues of oligosaccharide chains on the inhibitors. The most well-known source of neuraminidase used for this purpose is a so-called receptor-destroying enzyme. It has been shown by several groups that influenza A viruses lacking neuraminidase activity can undergo multiple cycles of replication in an in vitro infection system if bacterial neuraminidase is provided exogenously.