The Discovery of the Peptide may Inhibit Influenza Viruses

The Discovery of the Peptide may Inhibit Influenza Viruses

Flu rapidly spreads around the world in seasonal epidemics, killing millions of people in pandemic years and hundreds of thousands in nonpandemic years. It creates health care costs and lost productivity.


Three influenza pandemics in the 20th century, each following a major genetic change in the virus, killed millions of people all over the world. The world's current major influenza pandemic threat is H5N1; but it is at present mostly a flu in birds, not in people.

It is possible and in many cases recommended to get vaccinated against influenza with a flu vaccine. The 2006-2007 season is the first in which the U.S. CDC recommends that children (59 months) receive the annual flu vaccine.

The effectiveness of the flu vaccine is highly variable. Due to the high mutability of the virus, a particular flu vaccine formulation usually confers protection for no more than a few years. The World Health Organization co-ordinates the contents of the vaccine each year to contain the most likely strains of the virus that probably will attack the next year.

A fragment of a human protein that blocks influenza viruses -- including avian flu -- from attaching to and infecting cells holds promise if laboratory experiments are borne out, researchers said recently in a new study.

The discovery of the peptide by University of Wisconsin scientists, which published their findings in the Journal of Virology, may lead to an entirely new antiviral drug that could thwart H5N1 and other virulent flu strains that pose a threat of a global epidemic.

In tests on mice and in laboratory cultures, the molecule provided total protection against infection by influenza viruses, including H5N1. It also halted the spread of viruses in animals that were in the early stages of infection.

The molecule, known as an "entry blocker," is a fragment of a larger human protein that helps things pass through membranes such as those that encapsulate cells.

Though its precise mechanism is not fully understood, the peptide blocks the virus' ability to latch onto a key cell surface molecule it uses to get inside cells. To survive in a host, a virus needs to infect more cells to produce more infectious particles that spread to still more cells.

"It attacks a completely different part of the virus life cycle" than current antiviral drugs, said study co-author Curtis Brandt of the University of Wisconsin.

"The virus can't even get into the cell. The peptide is blocking the very earliest step in infection," he said in a statement.

Much work remains to determine how well a drug based on the molecule would work, the optimal dosage, and its safety, before it is tested on humans, the researchers said. It might become part of a drug "cocktail," much like those used to combat the AIDS virus.

Vaccines are considered the best defense against flu viruses, though a vaccine against H5N1 or some other virulent strain takes time to produce. Scientists fear avian flu will evolve into a form that passes easily from person to person and kill millions of people.

An antiviral based on the entry blocker could allow the body time to develop immunity to the viral particles that remain, the researchers said.

Current antiviral drugs do not cure a flu infection but are designed to reduce the number of days a person is sick and make the illness less severe.

There are already signs that the H5N1 virus can develop resistance to these drugs. There are two antiviral drugs known to work against H5N1 flu -- Roche Holding AG's and Gilead Sciences Inc's Tamiflu, known generically as oseltamivir, and GlaxoSmithKline's Relenza, known generically as zanamivir.

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