The mechanism through which antiviral drugs block influenza A has been identified by scientists at Iowa State University.
The study showed that these 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.
AdvertisementPrevious studies have shown that 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 study showed the drug attached to the surface of the virus protein near the proton channel and stopped the virus by indirectly changing the channel structure.
The new study led by Mei Hong showed that when amantadine is present at the pharmacologically relevant amount of one molecule per channel, it attaches to the lumen inside the proton channel.
Moreover, 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.
The virus begins an infection by attaching itself to a healthy cell. The healthy cell surrounds the flu virus and takes it inside the cell through a process called endocytosis. The virus then uses a protein called M2 to open a channel to the healthy cell.
Protons from the healthy cell flow through the channel into the virus and raise its acidity. That triggers the release of the virus' genetic material into the healthy cell. The virus hijacks the healthy cell's resources and uses them to reproduce and spread.
When amantadine binds to and blocks the M2 proton channel, the process doesn't work and a virus can't infect a cell and spread.
"Our study using solid-state nuclear magnetic resonance (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," Nature magazine quoted Hong as saying.
"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 chemists can now try to design new drugs to target the true binding site of the channel," Hong added.
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