The influenza virus

Influenza viruses are members of the orthomyxoviridae family which are further classified, on serological differences, into three distinct types, viz. A, B, and C. The human population appears to be most affected by types A and B [17], with the elderly, the very young and those with existing conditions such as chronic pulmonary and heart disease being most susceptible. 

Such genetic mixing is thought to occur in a susceptible animal (e.g. swine) infected with both human and avian influenza strains, resulting in a strain in which the avian surface proteins have replaced those of the human strain [7, 13,21,22], 

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Daniels, R.S., et al. Fusion mutants of the influenza virus hemagglutinin glycoprotein. Cell 40 431-439, 1985. 

Varghese, J.N., Laver, W.G., Colman, RM. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution. Nature 303 35-40, 1983. 

The influenza virus inhibitors, zanamivir, and oseltamivir, act outside the cell after virus particles have been formed. The dtugs have been designed to fit into the active site of the viral envelope enzyme neuraminidase, which is required to cleave sialic acid off the surface of the producing cells. When its activity is blocked, new virus particles stay attached to the cell surface through binding of the virus protein hemagglutinin to sialic acid and are prevented from spreading to other cells. 

Fig. 1 A view of the influenza virus haemagglutinin (HA) monomer with the receptor fragment a-2,3-sialyUactose [a-Neu5Ac-(2,3)- 3-Gal-(1,4)-P-Glc] bound...

Analysis of Potential Binding Interactions within the Influenza Virus Sialidase Active Site... 

Fig. 7 The influenza virus A sialidase active site showing the five potential inhibitor binding subsites (with S5 containing the hydrophobic pocket formed by reorientation of the Glu276 side-chain), with oseltamivir carboxylate 18 placed in the active site...

An interesting feature of the influenza virus sialidase active site that offers the potential for developing inhibitors specific for N1 sialidases, including avian influenza A/H5N1 virus sialidase, has recently been revealed by X-ray crystallography. The... 

Smith El, Palese P (1989) Variation in the influenza virus genes epidemiological, pathogenic and evolutionary consequences. In Krug RM (ed) The influenza viruses. Plenum, NY, pp 319-350... 

Varghese IN, Colman PM (1991) Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 A resolution. 1 Mol Biol 221 473 86 Varghese IN, Laver WG, Colman PM (1983) Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution. Nature 303 35 0 Varghese IN, McKimm-Breschkin IL, Caldwell IB, Kortt AA, Colman PM (1992) The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 14 327-332... 

The influenza virus possesses a neuraminidase that plays a key role in elution of newly synthesized progeny from infected cells. If this process is inhibited, spread of the vims is markedly diminished. Inhibitors of this enzyme are now available for use in treating patients with influenza. 

Treatment via chelation has been observed for 2-acetylpyridine thiosemi-carbazone derivatives, which have been found to possess inhibitory activity for the RNA-polymerases of the influenza virus [133]. The iron(III) complexes were shown to be 3 to 6 times more active as inhibitors of partially purified ribonucleotide reductase (no added iron) compared to uncomplexed thiosemi-carbazone [128]. Raina and Srivastava [134] prepared and characterized low spin iron(III) complexes of 2-acetylpyridine thiosemicarbazone, [Fe(8-H)2A] (A = NO3, OH, Cl, N3, NCS or NO2), which were proposed as being seven-coordinate. However, all but the azide complex are 1 1 electrolytes in DMF and their solid ESR spectra are rhombic with the g-values being about 2.20,2.15 and 2.00. Of the six complexes, the azide ion seems to interact ihost strongly with the iron(III) center. 

Prevention of pneumococcal disease by use of vaccination is a national goal Vaccination is used to prevent or minimize the severity of pneumonia caused by S. pneumoniae or the influenza virus. 

The discovery of pharmaceuticals commences with the scanning of hundreds of compounds, whether with actual materials (irrational approach) or virtual simulations (rational approach). To discover biopharmaceuticals, we have to examine the compounds within us, for example, hormones or other biological response modihers, and determine how they affect the biological processes. In some cases, we study pathogens such as the influenza virus or bacteria to derive the vaccines. In other cases, we copy these biological response modifiers and use them as replacement therapy. 

Discuss the structure and naming convention for the influenza virus. Provide reasons for the variations in the yearly compositions of the influenza vaccines. 

What are the characteristics that make the influenza virus, for example, avian influenza, a potential pandemic agent ... 

Carbon-carbon bond lyases, used in the reverse, synthetic direction have also enjoyed significant application in the pharmaceutical industry. For example 7/-acetyl-D-neuraminic acid (NANA), an intermediate in the chemoenzymatic synthesis of the influenza virus sialidase inhibitor zanamavir, may be synthesized using NANA aldolase. 

Immunopotentiating reconstituted influenza virosomes (IRTV) are spherical 150-nm sized particles consisting of a phospholipid bilayer in which influenza virus A/Singapore strain-derived hemagglutinin (HA) and neuraminidase (NA) are intercalated. As such, they resemble and mimic the influenza virus envelope. The difference from conventional liposome formulations lies in the inclusion of the viral envelope proteins HA and NA as well as viral phospholipids. Especially, the inclusion of influenza virus HA provides IRIV with delivery and immimogenic capacities. IRTV are licensed for human use as adjuvant in hepatitis A vaccination and as influenza subunit vaccine (1). 

For enveloped viruses such as the influenza viruses it has been shown that similar binding affinities are found for the hemagglutinin (HA) Hg-and sialic acid using either isolated HA or the whole virus [37,40] using simple H NMR titration experiments. In contrast to structural proteins of non-enveloped viruses, HA is a membrane protein and thus not as rigid as proteins as part of, e.g., icosahedral particles. For the application of STD NMR... 

Biosensors based on poly(diacetylene)s have also been investigated by other groups [51-54]. These have proved successful in detecting biologically relevant agents such as the influenza virus and cholera toxin. 

Simple imine formation was used in the formation of large DCLs directed toward inhibition of the enzyme neuraminidase by Eliseev and coworkers [11]. Neuraminidase is involved in the propagation of the influenza virus... 

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