Avian flu, or bird flu, has become a global health concern as it has spread rapidly through the world’s bird population in the last few years, endangering the well-being of humans who may come into contact with an infected bird. Among humans, bird flu typically manifests in a high fever, cough, sore muscles, and a sore throat. It often leads to severe respiratory crisis and, ultimately, death.

In general, avian flu is caused by any one of the Influenza A viruses, which are adapted to and hosted by birds, but which have the ability to infect other animals in close contact with diseased birds. In fact, the most recent massively deadly flu epidemic, which killed 50 million people worldwide in 1917, was caused by an Influenza A virus, H1N1. The specific agent of the current bird flu outbreak is H5N1, which is a subtype of the Influenza A virus.

The H5N1 virus is present in the saliva, mucous membranes, and feces of infected birds, and other birds may contract the virus through direct contact with these substances or with contaminated surfaces. While H5N1 is extremely contagious and deadly among birds, its transmission to humans has thus far been mostly limited to those with repeated and close contact with infected birds. However, the disease is very deleterious to the health of its human hosts, and it is susceptible to mutations that could make it transmittable from human-to-human. Such an occurrence could mark the beginning of a worldwide pandemic that could eventually kill millions of people.

Recently, Tamiflu®¹ and Relenza®², both antiviral drugs, have been used to treat humans infected with the H5N1 virus. However, the virus has already begun to show resistance to these compounds, underlining the need for rapid screening of drug candidates to keep pace with possible mutations to H5N1.

The D2OL project has chosen as its first avian flu target the H5N1 neuraminidase, which was implicated in the first known modern case of H5N1 human infection in Hong Kong in 1997. The H5N1 neuraminidase acts specifically by removing sialic acid residues from viral and cellular surfaces. Removal of sialic acid from the virus facilitates its release and prevents self-aggregation, which would inhibit its spread from cell to cell. In the host, sialic acid cleavage in the mucous linings of the airway clears the way for H5N1 invasion.

D2OL's target is believed to be critical in the life cycle of the H5N1 virus and drugs selected against it are expected to be viralcydal. With your help we are testing compounds that are readily available, and credible "hits" can be laboratory-tested against the neuraminidase to confirm potential utility fighting human infection.

Figure A represents the H5N1 neuraminidase; click on it to see details (graphic).