A structure- and NMR-based approach for the discovery of novel agents against Influenza A virus

MEDI 125

William H. Bisson, wbisson@burnham.org and Maurizio Pellecchia. Apoptosis/Infectious Diseases, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037
In the face of the persistent threat of human influenza A virus (H1N1) and the new mutated strains (H3N2), in addition to the recent outbreaks of avian influenza (H5N1) in Southeast Asia, there is an impending need for novel and effective supplies of anti-influenza virus agents. By using Nuclear Magnetic Resonance (NMR) spectroscopy we have studied a 25-residue peptide which is composed by the trans-membrane sequence amino acids of the viral M2 protein, an essential proton channel for viral maturation. Here we propose a combined approach utilizing in silico screening followed by NMR measurements for ligand binding studies and characterization. By using this approach, novel and specific agents against different strains of influenza A virus by directly targeting both wild-type and mutant M2 variants could be obtained. The combination of these data with a range of biochemical activities will provide a framework onto which to develop potentially novel anti-influenza therapies.
 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007