3-D pathogen model structure shows why there's no cure for the common cold

UW-Madison

Scientists at the University of Wisconsin-Madison have constructed a 3D model of rhinovirus C, published in the journal Virologthis week. Rhinovirus C is  seen as a ‘missing link’ cold virus. The team provide a topographical model of the capsid (protein shell) of a cold virus that was not identified until 2006.

Rhinovirus C is thought to be the pathogen responsible for almost half of all childhood colds. It is also a complicating factor for respiratory diseases like asthma. Rhinoviruses A, B and C are responsible for millions of illnesses that annually cost more than $40 billion in the United States alone.

The research is important as it constructs a very detailed structural model of the pathogen. This model shows that the protein shell of the virus is quite distinct from those of other strains of cold viruses. The structure goes some way toward explaining the previous failures of drug trials against rhinovirus.

Rhinoviruses A and B, including their three-dimensional structures, have long been known to science because they can be easily created and studied in the lab. Unfortunately Rhinovirus C is difficult to make as it resists culturing. The virus remained unidentified until 2006 when ‘gene chips’,  microchips that hold DNA probes that can recognise DNA from samples being tested, and advanced gene sequencing showed that the virus had been living in human cells with the A and B virus strains.

The new model of Rhinovirus C was built via computer simulation using advanced bioinformatics and the genetic sequences of 500 rhinovirus C genomes. These genomes provided the coordinates, in three dimensions, of the viral capsid. The result was a very high-resolution model.

With the completed structure there is an increased likelihood that drugs can be designed to effectively prevent colds from the rhinovirus C strain. Drugs that have proven to work against the A and B strains have been developed and advanced to clinical trials. Unfortunately their usefulness was somewhat stunted as they were constructed to take advantage of the surface features of the better known strains. The structures of those strains were resolved years ago through using X-ray crystallography.

These drug candidates failed. This was because the surface features that allow rhinovirus C to interlock with host cells and evade the immune system were not known, unlike those of rhinovirus A and B. The team of researchers predict that a rhinovirus C-specific drug will need to be created, as all the existing drugs tested on the virus did not work.

Antiviral drugs attach to and modify surface features of a virus. The drug must fit and lock into the virus; with no three-dimensional structure for rhinovirus C the pharmaceutical companies could not design appropriate drugs. Because rhinovirus C has a different receptor and a different receptor-binding platform, scientists must devise a different strategy to thwart the pathogen. 

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