The following tables show the decrease in the number of hospital visits needed, and the conditions suffered by this patient, once they were diagnosed and treated for their immune deficiency.
Introduction The avian influenza A virus H5N1 ; is highly pathogenic and has been shown to cross the species barrier and infect humans. Since its first emergence in Hong Kong in 1997 1 ; , the virulent H5N1 infections have caused many human deaths in various countries in Asia and Europe during the past few years. These events have led to global concern about a worldwide pandemic due to the possibility of antigenic shift allowing human-to-human transmission. The influenza A virus is a negative stranded RNA virus. Its surface contains two membrane glycoproteins, hemagglutinin HA ; and neuraminidase NA ; 2 ; . The HA functions as the receptor-binding and membrane fusion glycoprotein in cell entry, while the NA functions as the receptor-destroying enzyme by cleaving the -ketosidic linkage between terminal sialic acid and an adjacent sugar residue 3 ; . Influenza virus HA and NA are both glycosylated proteins, but the terminal sialic acids are released by the enzymatic activity of NA. The virus is further classified into subtypes based on i ; the subtype of the glycoproteins haemagglutinin and neuraminidase present on the virus and ii ; ability of the virus to cause disease. Currently, 15 haemagglutinin subtypes H1-H15 ; and nine neuraminidase subtypes N1-N9 ; have been identified for the influenza A virus 4 ; . Because of the essential role of NA in influenza replication and its highly conserved active site, the NA inhibitors were rationally designed to block this active site of the influenza virus. For the treatment or prophylaxis of influenza infections, the neuraminidase inhibitors are a new class of anti-influenza drugs that have antiviral activities against a broad range of influenza viruses. Several potent and specific inhibitors of the NA enzyme have been developed through structure-based rational drug design, and two inhibitors, zanamivir Relenza ; and oseltamivir Tamiflu ; , have been approved for human uses 5, 6 ; . Many crystal structures of an influenza virus complexed with their substrate and inhibitors have been determined 7-10 ; . Structure analysis of the NA enzyme demonstrated that there are several invariant residues which form part of active site center. Some of these residues interact directly with the substrate functional residues ; and others scaffold for the functional residues framework residues ; 11 ; . These residues include three arginines at positions 118, 292 and 371. The X-ray structures of N2 and N9 complexed with substrate and inhibitor show that these three residues form hydrogen bonds in the same manner with the carboxylate group of the sugar substrate and side chain of the inhibitor 2, 7, 9 ; . Other importance residues are E276 and E119, which were observed to form hydrogen bonds with the substrate 2 ; . It was also reported that interactions between zanamivir or oseltamivir and the residues in the NA active center are similar to those with the natural substrate 2 ; . Although the active sites of N2 and N9 are highly conserved, the inhibitory activity of oseltamivir leads to the mean IC50 of 1.9 to 2.7 nM and 9.5 to 17.7 nM, respectively 12 ; . A key question is why neuraminidase subtype N1 has a mean IC50 of 36.1 to 53.2 nM, significantly higher than those of N2 and N9 12 ; . Unfortunately, the X-ray structure of the OTV-H5N1 complex is not yet solved. The only information helping to understand this fact is the proposal of Moscona 13 ; based on the X-ray structure of oseltamivir and zanamivir complexed with neuraminidase N9. The active site of N1 was proposed to change its shape to accommodate the bulky side chain of oseltamivir, whereas such change is not required for zanamivir. This rearrangement involves the rotation of E276 and its bonding to R224 13 ; . To provide an answer to the above question, it is our intention to investigate structural, dynamic and thermodynamic properties as well as solvation of the three neuraminidase subtypes, N1, N2 and N9, complexed with oseltamivir using molecular dynamics simulations. Here, the and oxaprozin.