Researchers, including Indian-origin scientists, have discovered a new way to combat flu by identifying chemical agents that block the virus's ability to replicate itself in cell culture.
These novel compounds show promise for a new class of antiviral medicines to fight much-feared pandemic influenzas such as the looming "bird flu" threats caused by the H5N1 influenza A virus and the new H7N9 virus responsible for a 2013 outbreak in China.
Researchers said that some flu strains have developed resistance to Tamiflu, the sole orally available anti-flu drug.
Eddy Arnold from the Rutgers University and his collaborators have been working to create drugs beyond Tamiflu, especially ones that target different parts of the virus, using an approach that helped in the development of powerful anti-AIDS drugs.
By synthesising chemical compounds that bind to metal ions in a viral enzyme, the researchers could halt that enzyme's ability to activate a key step in the virus's replication process.
Arnold said his team's compounds "really gum up" the targeted enzyme of influenza virus.
The search for these binding compounds relies on technology that reveals the structure of this enzyme in extremely fine detail.
Researchers Joseph Bauman and Kalyan Das first produced high-resolution images of an H1N1 flu enzyme, and Bauman and postdoctoral researcher Disha Patel screened 800 small molecule fragments for binding.
The researchers in Arnold's lab worked with Edmond LaVoie, professor and chair of medicinal chemistry in the Ernest Mario School of Pharmacy, to modify those compounds, making them more potent and selective in blocking the flu enzyme's activity.
Working with virologist Luis Martinez-Sobrido at the University of Rochester, they were able to detect antiviral activity of the compounds in cells.
The enzyme that the scientists are attacking is especially crafty, Arnold noted, because it steals material from human cells to disguise the invading flu virus in a process called "cap-snatching."
These "caps" are a small chemical structure that prime the process for reading genetic information.
"What we're doing by blocking or inhibiting this enzyme is to interfere with flu's ability to disguise itself," he said.
The study was published in the journal ACS Chemical Biology.