National Geographic : 2010 Jan
the human cell that helps the virus reproduce, though, could stop it with little risk of resistance. "And if you can identify a host function that HIV, flu, and Ebola all require, you can have one drug that is active against all three---a broad-spectrum antiviral," says Michael Kurilla of the National Institute of Allergy and Infectious Diseases (NIAID). The key is finding the right target---a gene, and the protein it encodes, that the human cell doesn't need but the virus does. Human DNA contains more than 20,000 genes, but in any given cell at any given time, many are dormant; some, for instance, are only switched on during embryonic development. With the human genome now fully decoded, investigators can search for targets systematically by disabling individual genes in many cells and seeing what happens. Zirus, a company in Buford, Georgia, uses a three-step process (see opening illustration); it begins by infecting cells with a harmless retrovirus, which splices itself randomly into human DNA, knocking out any gene it interrupts. Other groups are disabling selected genes with matching bits of RNA. If the cell survives without a particular gene and is now resistant to infection, that gene-protein combo is a promising target for a drug. The first such drug, Pfizer's Maraviroc, is already being used to treat HIV infections; it blocks a cell-surface protein that acts as a receptor for the virus. San Diego--based NexBio has recently begun clinical trials of a compound called Fludase that inactivates the receptors through which both swine flu and seasonal flu enter respiratory cells. NIAID is vigorously supporting such research. "Over the next 20 to 30 years there will be a paradigm shift in the way we approach infectious diseases," Kurilla says. "I think this will be emblematic of 21st-century medicine." ---Josie Glausiusz THE BIG IDEA (continued) HOST CELL Nucleus Receptor Viral protein Genes Protein coat CONVENTIONAL DRUG VIRUS NEW DRUG A B C D Conventional antiviral drugs target the virus itself. For example, Tamiflu blocks a surface protein on the influenza virus that enables it to escape from one cell to infect another. A INVADE CELL Proteins on the surface of the virus bind to receptors on the host cell. The virus fuses with the cell. How viruses use a host cell to replicate B UNCOAT Human enzymes dissolve the virus's protein coat, releasing the genes in its core. C MULTIPLY The virus takes over the host cell's machinery to make copies of its genes and proteins. D GO FORTH The genes and the proteins form new viruses, which bud from the cell and seek new hosts. 4 BREAK THE CYCLE A virus's life cycle could be disrupted at different stages by a drug that targets a human protein. The only such drug approved so far blocks a receptor that HIV needs to enter human immune cells.