October 30, 2013
Rhinovirus C Structure Has Inhibited Search For Common Cold Cure
[ Watch the Video: Human Rhinovirus C15 Model Suggests Novel Topography ]
redOrbit Staff & Wire Reports - Your Universe OnlineThanks to the genetic sequencing of the so-called “missing link” cold virus, researchers have created a three-dimensional model of the pathogen that sheds new light on why there is currently no cure for the common cold.
Writing in Monday’s edition of the journal Virology, University of Wisconsin-Madison biochemistry professor Ann Palmenberg and her colleagues created a topographical model of the protein shell (or capsid) of rhinovirus C, a type of cold virus that was unknown to the medical community until seven years ago.
According to the study authors, rhinovirus C is believed to be responsible for as many as half of all colds among children, and is also considered to be a serious complicating factor for asthma and other respiratory ailments. Rhinovirus C, along with the A and B versions of the same pathogen, are reportedly the cause of millions of illnesses each year, with an annual cost topping $40 billion dollars in the US alone.
The research is described as important, as it creates an exceptionally detailed structural model of the cold virus and demonstrates that it has a different protein shell than other strains of cold viruses. Palmenberg said that the discovery “explains most of the previous failures of drug trials against rhinovirus.”
“The A and B families of cold virus, including their three-dimensional structures, have long been known to science as they can easily be grown and studied in the lab,” the university explained in a statement. “Rhinovirus C, on the other hand, resists culturing and escaped notice entirely until 2006 when ‘gene chips’ and advanced gene sequencing revealed the virus had long been lurking in human cells alongside the more observable A and B virus strains.”
The new cold virus model was constructed using a computer simulation, and took advantage of both advanced bioinformatics and the genetic sequences of 500 rhinovirus C genomes – the latter of which provided the three-dimensional coordinates of the viral capsid, the investigators said.
Previously, pharmaceutical firms attempting to design drugs to combat the common cold had little to work with due to the lack of a 3D rhinovirus C model. Palmenberg, who was a member of the team that first mapped the genomes of all known common cold viruses in 2009, called it a “very high-resolution model” that “fits the data.”
“With a structure in hand, the likelihood that drugs can be designed to effectively thwart colds may be in the offing,” the university said. “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.”
Since all three cold virus strains contribute to the illness, potential medicines developed to combat the common cold failed. This is because drug makers did not fully understand the surface features which allowed rhinovirus C to dock with host cells and avoid a person’s immune system .
Those features are different in rhinovirus C than they are in A and B, and none of the drugs tested by the research team were found to be effective. For that reason, the authors have concluded that pharmaceutical firms will need to develop a substance that specifically targets rhinovirus C – a feat which should now be possible, thanks to the 3D rhinovirus C model produced through their efforts.
Image 2 (below): Two faces of the common cold. The protein coat of the “missing link” cold virus, Rhinovirus C (right), has significant differences from the more observable and better studied Rhinovirus A. Those differences explain why no effective drugs have yet been devised to thwart the common cold.