AMES, Iowa Antiviral drugs block influenza A viruses from reproducing and spreading by attaching to a site within a proton channel necessary for the virus to infect healthy cells, according to a research project led by Iowa State University's Mei Hong and published in the Feb. 4 issue of the journal Nature.
Hong, Iowa State's John D. Corbett Professor of Chemistry and an associate scientist for the U.S. Department of Energy's Ames Laboratory, said the findings clarify previous, conflicting studies and should pave the way to development of new antiviral drugs against influenza viruses, including pandemic H1N1.
Two papers published by Nature in 2008 came to different conclusions about where the antiviral drug amantadine binds to a flu virus and stops it from infecting a healthy cell. A paper based on X-ray studies concluded the drug attached to the lumen of the proton channel, the area inside the channel, and stopped the virus by blocking the channel. Another paper based on solution nuclear magnetic resonance (NMR) technology concluded the drug attached to the surface of the virus protein near the proton channel and stopped the virus by indirectly changing the channel structure.
Hong's research concluded that when amantadine is present at the pharmacologically relevant amount of one molecule per channel, it attaches to the lumen inside the proton channel. But the paper also reports that when there are high concentrations of amantadine in the membrane, the drug will also attach to a second site on the surface of the virus protein near the channel.
"Our study using solid-state NMR technology unequivocally shows that the true binding site is in the channel lumen, while the surface-binding site is occupied only by excess drug," Hong said. "The previous solution NMR study used 200-fold excess drug, which explains their observation of the surface-binding site. The resolution of this controversy means that medical
|Contact: Mei Hong|
Iowa State University