Model virus structure shows why there's no cure for common cold

October 28, 2013 by Terry Devitt, University of Wisconsin-Madison
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 surface differences, revealed in a new three-dimensional model of Rhinovirus C from the UW–Madison lab of Ann C. Palmenberg, explain why no effective drugs have yet been devised to thwart the common cold. Credit: University of Wisconsin-Madison

In a pair of landmark studies that exploit the genetic sequencing of the "missing link" cold virus, rhinovirus C, scientists at the University of Wisconsin-Madison have constructed a three-dimensional model of the pathogen that shows why there is no cure yet for the common cold.

Writing today (Oct. 28, 2013) in the journal Virology, a team led by UW-Madison biochemistry Professor Ann Palmenberg provides a meticulous topographical model of the capsid or protein shell of a that until 2006 was unknown to science.

Rhinovirus C is believed to be responsible for up to half of all childhood colds, and is a serious complicating factor for respiratory conditions such as asthma. Together with rhinoviruses A and B, the recently discovered virus is responsible for millions of illnesses yearly at an estimated annual cost of more than $40 billion in the United States alone.

The work is important because it sculpts a highly detailed structural model of the virus, showing that the protein shell of the virus is distinct from those of other strains of cold viruses.

"The question we sought to answer was how is it different and what can we do about it? We found it is indeed quite different," says Palmenberg, noting that the new structure "explains most of the previous failures of drug trials against ."

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. 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 built "in silico," drawing on advanced bioinformatics and the genetic sequences of 500 rhinovirus C genomes, which provided the three-dimensional coordinates of the viral capsid.

"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 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 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 , 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."

Explore further: Toward broad-spectrum antiviral drugs for common cold and other infections

Related Stories

Toward broad-spectrum antiviral drugs for common cold and other infections

June 26, 2013
Scientists are reporting progress in the search for the first broad-spectrum drugs to combat human rhinoviruses (HRVs), which cause humanity's most common infectious diseases. Their study on these potential drugs for infections ...

Asymptomatic rhinovirus infection outnumbers symptomatic infection 4 to 1 among university students

June 19, 2012
The common cold virus may be more common than previously thought in university students not reporting any symptoms. Rhinovirus, the virus responsible for the common cold was found at some point during an 8-week study period ...

Cold sore linked to mutation in gene, study suggests

September 16, 2013
Why some people are troubled by cold sores while others are not has finally been explained by scientists.

Why we don't become immune to colds

March 8, 2012
A team of researchers at the MedUni Vienna has discovered why we never become immune to colds, and why we are able to keep catching them: the MedUni Vienna study, published in The FASEB Journal in the USA by Katarzyna Niespodziana ...

Recommended for you

Scientists uncover new gatekeeper function of anti-aging molecule

November 12, 2018
The protein klotho has been shown to promote longevity and counteract aging-related impairments. Having more klotho seems to allow for longer and healthier lives, whereas a depletion of this molecule accelerates aging and ...

Can scientists change mucus to make it easier to clear, limiting harm to lungs?

November 12, 2018
For healthy people, mucus is our friend. It traps potential pathogens so our airways can dispatch nasty bugs before they cause harm to our lungs. But for people with conditions such as cystic fibrosis (CF) and chronic obstructive ...

Mutations, CRISPR, and the biology behind movement disorders

November 12, 2018
Scientists at the RIKEN Center for Brain Science (CBS) in Japan have discovered how mutations related to a group of movement disorders produce their effects. Published in Proceedings of the National Academy of Sciences, the ...

Researchers explain how your muscles form

November 12, 2018
All vertebrates need muscles to function; they are the most abundant tissue in the human body and are integral to movement.

Defective DNA damage repair leads to chaos in the genome

November 12, 2018
Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now found a cause for frequent catastrophic events in the genetic material of cancer cells that have only been known for a few ...

Salmonella found to be resistant to different classes of antibiotics

November 12, 2018
Brazil's Ministry of Health received reports of 11,524 outbreaks of foodborne diseases between 2000 and 2015, with 219,909 individuals falling sick and 167 dying from such diseases. Bacteria caused most outbreaks of such ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.