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.
Eddy Arnold, Board of Governors Professor of chemistry and chemical biology in the School of Arts and Sciences at Rutgers and a member of the Center for Advanced Biotechnology and Medicine observed that some flu strains have developed resistance to Tamiflu, the sole orally available anti-flu drug.
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."
He said that these "caps" are small chemical structure that prime the process for reading genetic information.
The findings have been published in the American Chemical Society journal ACS Chemical Biology.