Utrecht researchers clarify structure of key protein in coronaviruses

Coronavirus can cause mild to serious infections of the respiratory tract or the digestive systems of animals and humans. In collaboration with researchers in France and America, scientists at the Virology Department of Utrecht University’s Faculty of Veterinary Medicine have unravelled the structure of an important protein that these viruses use to penetrate their target cells. Their conclusions will be published soon in the journal Nature.

Coronaviruses are very common in humans and in animals. They cause mild to serious infections of the respiratory tract or the digestive systems of animals and humans. At least six different coronaviruses have been identified for humans, of which the deadly SARS and MERS coronaviruses are perhaps best known.

Penetrating cells
In order to successfully infect an organism, the viruses have to insert their genetic material (RNA) into the target cell. This is often done via the epithelial (surface) cells of the respiratory or digestive systems. The viruses bind to the cells using a surface protein called a ‘spike’ protein. The viruses then allow their outer membrane to be absorbed by the cell membrane, which releases the viral RNA into the cell. In the coronavirus, the spike protein is responsible for both binding with the cell and the fusion of the two membranes.

New insights
The co-authors of the article in Nature, Utrecht University researchers Dr. Berend Jan Bosch and Prof. Peter Rottier, began their studies of the structure of the spike protein in 1998. Together with colleagues from the Institut Pasteur in Paris, they try to understand the protein using protein crystallisation, but their efforts were consistently unsuccessful. After years of unsuccessful attempts, they have recently managed to clarify the structure of the spike protein. This detailed knowledge will provide important new insights into the mechanisms behind these two processes of infection.  

Clarifying the protein structure
Together with researchers from the University of Washington in Seattle (USA), they applied new techniques from the field of electron microscopy in order to clarify the complex structure of the protein. The results not only provide new fundamental insights into the process of infection, but also offer new starting points for developing targeted strategies for treatment or prevention of the infections.

The study has been published in Nature, and is available here.

Left: electron microscope image of coronavirus with 'spikes' used to penetrate the host cell membrane. Right: spike protein, consisting of three copies of the spike glycoprotein. Middle: impression of spikes on the surface of the virus.