Generally anti-flu drugs, such as oseltamivir (Tamiflu) and zanamivir (Relenza) work by blocking neuraminidase, a glycoprotein found on the influenza virus surface. Two types of neuraminidase are present in influenza A virus: group 1 and group 2. Both Tamiflu and Relenza were developed using a subset of group 2 structures, which were the only neuraminidase structures known at the time of their development. At the BCCA, researchers have recently computationally identified 30 known candidate drugs as strong competitive binders to group 1 influenza neuraminidases (which encompasses the H5N1 strain), and screened and identified 115 novel compounds sourced from NCI and Chembridge compound libraries that bind with equal or superior docking properties compared to Tamiflu. The BCCA has also identified 2 drug candidates that bind to Influenza A Nucleoprotein and an additional 26 novel compounds sourced from the NCI compound libraries that bind with high docking energy. All candidates in this suite of compounds, collectively referred to as Avi-Flu ONETM compounds,are believed not only to be potential therapeutic agents against avian flu, but potentially other diseases and disorders as well, and as such the BCCA has filed provisional patents on this technology.

The current outbreaks of pathogenic avian influenza, which began in South-East Asia and now impacts eight Asian Nations, are the largest in the history of this disease. The H5N1 virus, the causative agent of this disease, has proven to be especially persistent; now considered endemic in many parts of Indonesia and Viet Nam in addition to portions of Cambodia, China, and Thailand. The highly pathogenic H5N1 strain of avian influenza is emerging as the most likely cause of the world’s next major influenza pandemic. Since the first reports of this virus crossing from poultry to humans in January 2004, recent outbreaks have extended the range of the virus in infected birds from Asia to Europe and Africa. The continuing presence of the influenza A/H5N1-virus is of concern because of the risk of its recombination with human influenza strains and/or its adaptation to humans by continuous mutation which could create a pandemic strain. Given that the H5N1 virus has resulted in more human death and disease than any other form of avian influenza virus, anti-flu drugs are being tested as potential therapeutic candidates. With case-fatality rates for human cases to date averaging 61% an H5N1 pandemic could potentially be far worse than historical type A influenza pandemics such as the avian flu-related H1N1 pandemic of 1918 (this claimed 50 million lives with a case fatality rate of 2-3 %).

Presently, the BCCA is conducting validation studies to confirm inhibitory activity of these compounds in industry-standard viral replication assays. Given that some of the compounds in the portfolio are known drugs it is expected that development and regulatory costs will be minimized.