UTMB, BCM contracted to test avian flu drugs

HOUSTON -- (November 4, 2005) -- The National Institute of Allergy and Infectious Diseases of the National Institutes of Health has awarded scientists at The University of Texas Medical Branch a $1.4 million contract to study how well antiviral products work to treat or prevent naturally occurring influenza infections - one of them the H5N1 virus, which often causes lethal disease in infected people.

Although it does not yet appear to be easily transmitted between people, scientists fear that the H5N1 bird flu strain may soon evolve, potentially triggering an extremely deadly global epidemic known as a pandemic.

If the virus mutates to allow it to be contagious from person to person, "we're afraid it could be as serious as the 1918-1919 influenza pandemic, which is estimated to have killed more than 20 million people worldwide," said Slobodan Paessler, project leader for the UTMB flu testing contract.

BCM researchers Robert B. Couch, M.D., and Philip R. Wyde, Ph.D., professors of molecular virology and microbiology, will collaborate in the research, along with UTMB respiratory disease researchers led by Norbert J. Roberts, M.D., professor of internal medicine specializing in infectious diseases.

Two classes of antiviral drugs are used to treat influenza virus infection, and both are being tested in the UTMB project: M2 inhibitors, which are believed to block early replication of the virus, and neuraminidase (NA) inhibitors, which hinder the enzymatic activity of NA that is believed necessary for the virus to reach its target cells. Amantadine and rimantadine are in the first category and have been used effectively to treat influenza A virus infections for many years. Studies have shown a low incidence of resistance to these drugs among currently circulating influenza viruses. But their use is rising worldwide, and drug resistance has been reported among influenza A (H5N1) viruses isolated from both poultry and human beings in Asia. The high frequency of resistant viruses where these drugs have been used extensively over time suggests that their future usefulness will be limited.

Last May, a World Health Organization expert panel also warned of partial H5N1 viral resistance to the NA inhibitor oseltamivir. In preparation for a possible pandemic, experts say, it is critically important to evaluate various antiviral drugs that may be of therapeutic use, not only to check for viral resistance but also so the medications may be used as an alternative to existing drugs to treat influenza. Studies under this contract will evaluate currently licensed and new influenza drugs.

The year-long UTMB project includes plans to test the drugs oseltamivir, peramivir and amantidine in ferrets, animals often used in similar flu studies because they are believed to best reflect human influenza. Oseltamivir and amantadine are licensed, commercially available prescription products; peramivir has not yet been licensed for human use by the Food and Drug Administration. The drugs will be administered orally and, in the case of peramivir, intramuscularly as well, both before and after separate groups of animals have been infected with either the less-lethal H3N2 strain of flu or the H5N1 strain.