Influenza virus, spread

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. 

Neuraminidase inhibitors are the major class of drugs to treat or to prevent the infection with influenza viruses. Currently, two neuraminidase inhibitors are available, zanamivir and oseltamivir, which block the release of new influenza vims from infected host cells and thereby stop the spread of infection. The enzyme neuraminidase is a surface glycoprotein present on all influenza viruses. There are nine influenza neuraminidase sub-types known of which subtypes N1 and N2 appear to be the most important ones. Neuraminidase inhibitors are effective against all neuraminidase subtypes. The activity of the neuraminidase is required for the newly... 

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. 

Certain types of infechous agent (e.g. influenza virus) are able to combat herd immunity sueh as this through undergoing major antigenic changes. These render the majority of the population susceptible, and their occurrence is often aeeompanied by spread of the disease aeross the entire globe (pandemies). 

Mechanism of Action A selective inhibitor of influenza virus neuraminidase, an enzyme essential for viral replication. Acts against both influenza A and B viruses. Therapeutic Effect Suppresses the spread of infect ion within the respiratory system and re-duces the duration of clinical symptoms. 

If all the sugar residues of the glycophorin molecules in an erythrocyte were spread over the surface of the cell they could cover approximately one-fifth of its surface in a loose network. However, it is more likely that they form bushy projections of a more localized sort. These oligosaccharides not only act as immunological determinants but also serve as receptors for influenza viruses. Other glycoproteins related to glycophorin A occur in smaller amounts.244... 

The worldwide spread of H5N1 avian influenza virus has raised the concern of its potential to emerge as a human-adapted virus. Three decades of intense research have yielded only two NA inhibitors, Relenza and Tamiflu , that... 

Pathogens can be spread from person to person in a number of ways. Not all pathogens use all the available routes. For example, the influenza virus is transmitted from person to person through the air, typically via sneezing or coughing. But the virus is not transmitted via water. In contrast, Escherichia coli is readily transmitted via water, food, and blood, but is not readily transmitted via air or the bite of an insect. 

Special interest has been taken in the inhibition of enzymes involved in cleaving the glycosidic bonds of neuraminic acid (a complex C9-carbon sugar acid), because this process is critical to the spread of infection after the influenza virus binds to the host cell. Following the analysis of the structure of complexes of the enzyme and substrate (bound in a distorted conformation), unsaturated compounds, for example 43 (Figure 1.14), were made as mimics of the latter in the reaction transition state and found to be potent neuraminidase inhibitors and anti-influenza compounds [49]. 

All viral respiratory tract infections occur more commonly in the winter, and rapid person-to-person spread through susceptible populations is typical. Underlying cardiac or pulmonary disease predisposes to an increased incidence and severity of viral lower respiratory tract infection, especially with influenza virus in adults and RSV in children. Radiographic findings are nonspecific and include bronchial wall thickening and perihilar and diffuse interstitial infiltrates. Pleural effusions may be seen, especially in adenovirus and parainfluenza pneumonia. 

Influenza neuraminidase cleaves terminal sialic acid residues and destroys the receptors recognized by viral hemagglutinin, which are present on the cell surface, in progeny virions, and in respiratory secretions. This enzymatic action is essential for release of virus from infected cells. Interaction of oseltamivir carboxylate with the neuraminidase causes a conformational change within the enzyme s active site and inhibits its activity. Inhibition of neuraminidase activity leads to viral aggregation at the cell surface and reduced virus spread within the respiratory tract. 

Migratory water birds are primary hosts for the influenza virus, which they spread to domestic birds. Genetic rearrangement takes place and produces viruses that can be transmitted to humans. An outbreak in China in 1997 provides a striking example of how the process works. The deadly strain of influenza that appeared at that time was a combination of three viral strains from quail, geese, and teal from mainland China. Genetic recombination took place in the... 

In addition, occasional pandemic outbreaks are a fatal threat About 50 mUhon people died in the pandemic outbreak of 1918 (56), further pandemics occurred in 1957 and 1968. High mutation rates of the influenza virus and the occurrence of new influenza strains are major obstacles in fighting influenza. Therefore, a serious threat is caused by avian influenza strains (57). Avian influenza is now common in Southeast Asia and is spreading fast. Infected birds have been found in Europe and Africa. Avian influenza barely infects humans until now and it only transmits from birds to humans, if humans have very close contact to infected birds. However, in contrast to human influenza, the death rate for humans infected with avian influenza is exceptionally high. A new influenza strain might arise from recombination of human and avian or mutation of avian influenza strains alone that is as lethal as avian and as infectious as human influenza (58-60). 

Droplet spread Healthcare workers, patients Staphylococcus aureus Respiratory syncytial virus Influenza virus... 

Every year we face an outbreak of influenza (the flu). Most of the time it is a virus that is already present in the population and therefore can be controlled by flu shots. But every once in awhile, a new influenza virus appears, which can cause a worldwide pandemic because it is not affected by any immunity a person may have to older strains of influenza and can therefore spread rapidly and infect a large number of people. And almost no effective antiviral drugs are available for the flu. (See Tamiflu on page 1124.)... 

Influenza usually begins in the community and, like respiratory syncytial virus, spreads to the hospital from infected patients, staff, or visitors (2,174). Influenza is spread person to person by large droplet nuclei introduced into the respiratory tract of close contacts, but direct contact transmission may also occur. Closed units such as nursing homes, chronic disease facilities, intensive care units, and pediatric wards predispose to increased risk. Influenza is usually diagnosed clinically and confirmatory cultures, if done, are performed on the first cases. 

Calyceramides A-C, isolated from Discodermia calyx harvested in Japan, are inhibitors of neuraminidase, an enzyme on the surface of the influenza virus, which acts during the process of the spread of viral infection by degrading glycoconjuguates of sialic acid (N-acetylneura-minic acid). Neuraminidase inhibitors are rare, and sul-fated ceramides could be good models for study (Nakao et al., 2001). 

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