Navigation Links
Model virus structure shows why there's no cure for common cold
Date:10/28/2013

MADISON, Wis. 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 cold virus 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 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. 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 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
acpalmen@wisc.edu
608-262-7519
University of Wisconsin-Madison
Source:Eurekalert

Related biology news :

1. First model of how buds grow into leaves
2. Parkinsons disease stopped in animal model
3. New method for estimating parameters may boost biological models
4. Bone marrow transplant arrests symptoms in model of Rett syndrome
5. 3-D RNA modeling opens scientific doors
6. NCEAS researchers offer new ecological model for deep-water oil spills
7. Patel recognized with NSF Career Award for computer-modeling research on cell membranes
8. Model forecasts long-term impacts of forest land-use decisions
9. A cells first steps: Building a model to explain how cells grow
10. Computer model pinpoints prime materials for efficient carbon capture
11. The academic jungle: Ecosystem model reveals why women are driven out of science
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/28/2016)... JOSE, Calif., Jan. 28, 2016 Synaptics (NASDAQ: SYNA ... results for its second quarter ended December 31, 2015. ... second quarter of fiscal 2016 increased 2 percent compared to the ... second quarter of fiscal 2016 was $35.0 million, or $0.93 per ... Non-GAAP net income for the first quarter of fiscal 2016 grew ...
(Date:1/22/2016)... , January 22, 2016 /PRNewswire/ ... announced the addition of the  "Global ... their offering. --> http://www.researchandmarkets.com/research/4lmf2s/global_behavioral ... the  "Global Behavioral Biometric Market 2016-2020" ... Research and Markets ( http://www.researchandmarkets.com/research/4lmf2s/global_behavioral ) ...
(Date:1/20/2016)... 20, 2016   MedNet Solutions , an innovative ... of clinical research, is pleased to announce the attainment ... are the result of the company,s laser focus on ... , it,s comprehensive, easy-to-use and highly affordable cloud-based ... Key MedNet growth achievements in 2015 include: ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... HOUSTON , Feb. 9, 2016 /PRNewswire/ ... virus-driven immunotherapies for cancer, announced that its ... the European Commission as an orphan medicinal ... the deadliest form of glioma, strikes approximately ... and EU. http://photos.prnewswire.com/prnh/20160208/330986LOGO ...
(Date:2/9/2016)... , Feb. 9, 2016 ... Insights, 2016", report provides in depth insights ... activities around the Protein-Tyrosine Phosphatase 1B (PTP1B) ... profiles in various stages of development including ... Phase III and Preregistration. Report covers the ...
(Date:2/8/2016)... N.C. , Feb. 8, 2016 Novan, Inc. today ... Chairman of the Board of Directors of Novan. In addition, ... North Carolina . --> ... Company also announced that it received a total of $32.8 million ... 2015 from its private investor network originating throughout the Research Triangle ...
(Date:2/8/2016)... ... February 08, 2016 , ... Franz Inc. , an ... technology, today announced the availability of AllegroGraph 6, the leading Semantic Graph Database ... Certified Technology Program (CCPT). AllegroGraph is the first Semantic Graph Database to ...
Breaking Biology Technology: