It was only in 2006 that researchers discovered the latest of three major viruses known to cause the common cold. Now, a new 3-D model of this pathogen, the nastiest of the rhinoviruses, may help pave the way to more effective cold remedies.
Ann Palmenberg, a biochemist at the University of Wisconsin–Madison, and her colleagues constructed the model of rhinovirus C to better understand how all rhinoviruses (species in the genus Enterovirus) work, grow and react. “It explains a lot of the missing biology, if you will,” she says. The findings were published in the January 5 issue of Virology.
The model reveals that the capsid, or protein shell, of rhinovirus C differs from those of rhinoviruses A and B, for which 3-D models are already known. A capsid, or protein shell, encases a virus and allows it to attach to a host cell. Understanding the structure of a capsid allows researchers to create antivirals that can latch onto the pathogen’s protein shell.
That finding also explains why treatments for rhinoviruses A and B that succeeded in the lab later failed in clinical trials. In addition to other complications it is thought that patients in clinical trials carried a rhinovirus C strain along with A and B, so drugs designed to tackle only the latter types had no impact on what is now understood to be a very different rhinovirus C species.
Palmenberg was part of a team that sequenced rhinovirus C’s genome in 2009, creating a blueprint for what would become the model. “It turns out that the Cs, unlike the As and Bs, have deletions in a very crucial capsid protein,” Palmenberg says. “We got lucky in the way nature designed its sequence.”
Rhinovirus C is thought to cause half of all childhood colds. Estimates show that all rhinoviruses are responsible for millions of illnesses each year, totally about $40 billion in lost productivity in the U.S. alone. “It turns out that the Cs are really nasty,” Palmenberg says. “They're the ones that make kids the sickest and they're the ones that trigger asthma expiration.”
Knowledge of the structure of the capsid should help scientists get closer to designing specific drugs to combat rhinovirus C. “One of the things structures would be used for would be to rationally design inhibitors that might act as antivirals,” says John Treanor, chief of the Infectious Diseases Division at the University of Rochester Medical Center. Inhibitors prevent viruses from attaching to host cells.
Palmenberg says that all strains of rhinovirus C appear similar, as is the case with A and B strains as well. “So if something that works against a C—it will take out all of the Cs,” she says. “So that's the good news. The bad news is that the existing drugs won't do it.”