New Molecular Way To Combat The Flu

Hong Kong microbiologists have uncovered a new protein target for treating influenza A, along with a small molecule that prevents viral replication by blocking the protein (Nat. Biotechnol., DOI: 10.1038/nbt.1638). Richard Y. Kao of the University of Hong Kong and coworkers used a forward chemical genetics approach to identify influenza A nucleoprotein as a drug target. The researchers then screened a library of more than 50,000 compounds, taking a closer look at molecules that were effective at preventing degenerative changes in cells caused by nucleoprotein and at how well molecules blocked accumulation of nucleoprotein in the nucleus of cells. They zeroed in on one compound, nucleozin, for further study because of its promising antiviral activity and optimal solubility. Kao’s team showed that nucleozin is effective against H1N1, H3N2, and H5N1 flu strains. The compound worked in cell culture and in mice, with nucleozin-treated animals showing a 10-fold reduction of viral load in the lungs compared with untreated animals. Finding new forms of treatment for the flu is important, the researchers point out, especially as more virulent strains emerge or as viruses develop resistance to current therapies, such as Tamiflu, a small-molecule drug that also interferes with viral replication.