"It's a very high-resolution model," notes Palmenberg, whose group along with a team from the University of Maryland was the first to map the genomes for all known common cold virus strains in 2009. "We can see that it fits the data."
With a structure in hand, the likelihood that drugs can be designed to effectively thwart colds may be in the offing. Drugs that work well against the A and B strains of cold virus have been developed and advanced to clinical trials. However, their efficacy was blunted because they were built to take advantage of the surface features of the better known strains, whose structures were resolved years ago through X-ray crystallography, a well-established technique for obtaining the structures of critical molecules.
Because all three cold virus strains all contribute to the common cold, drug candidates failed as the surface features that permit rhinovirus C to dock with host cells and evade the immune system were unknown and different from those of rhinovirus A and B.
Based on the new structure, "we predict you'll have to make a C-specific drug," explains Holly A. Basta, the lead author of the study and a graduate student working with Palmenberg in the UW-Madison Institute for Molecular Virology. "All the [existing] drugs we tested did not work."
Antiviral drugs work by attaching to and modifying surface features of the virus. To be effective, a drug, like the right piece of a jigsaw puzzle, must fit and lock into the virus. The lack of a three-dimensional structure for rhinovirus C meant that the pharmaceutical companies designing cold-thwarting drugs were flying blind.
"It has a different receptor and a different receptor-binding platform," Palmenberg explains. "Because it's different, we have to go after it in a different way."
|Contact: Ann C. Palmenberg|
University of Wisconsin-Madison