As long as there is neither a vaccine nor a drug against the new coronavirus SARS-CoV-2, quarantine measures can only be taken to prevent the spread of this highly contagious disease. An important step in the search for a suitable active ingredient is to decipher the exact molecular structure of the virus. At the BESSY II X-ray light source at the Helmholtz Zentrum Berlin, researchers have now investigated a protein that is essential for the virus to multiply. In an interview with Welt der Physik, Manfred Weiss, head of the group for macromolecular crystallography at the research center, explains how such an analysis works and what results it gave.
World of physics: Why is it important to know the three-dimensional structure of certain proteins in the virus?
Manfred Weiss: The gene sequence of the virus has been known since January. Shortly after the outbreak of the disease, scientists in China were able to determine it using genetic methods. From the pure sequence of amino acids, however, neither the function nor the weak points of the proteins – regardless of whether they are viruses or human proteins – can be understood. Only when the amino acids have “put together” in a complex folding process to form the finished protein with a complex three-dimensional structure can they become biologically active.
How do you decipher the structure of these complex macromolecules from hundreds of amino acids?
We analyze the structure using protein crystallography. The proteins are examined with a very intensive X-ray laser. Since you would not see anything with a single protein, you need a lot of proteins, which you first grow into crystals that are arranged as evenly as possible. This is very difficult, especially with complex proteins. If you then examine the protein crystals with the highly brilliant X-ray light at our BESSY II system, the exact structure of the proteins can be calculated on the computer from the images obtained. However, we do not do this work, but the working groups of the various institutes, to whom we provide our accelerator infrastructure.
What can be learned from such three-dimensional images?
In the case of a successful protein analysis, you then know with more or less atomic accuracy which atom is in which position. From this you can determine, for example, the so-called active center. That is the crucial point of a protein at which certain biochemical reactions are initiated. Of the more than 3,000 protein structures that we have been able to uncover in the past few years, about half are bacteria and viruses. This is becoming increasingly important for drug development and makes it much easier to find suitable active ingredients.
What have the researchers who examined the new corona virus found out?
The scientists have succeeded in deciphering the structure of a central component of the virus, the so-called main viral protease. This protease is a kind of molecular scissors. When the virus infiltrates a cell’s genome, the virus causes it to produce viral proteins. Initially, these are still connected in one piece and are not functional. The protease now cuts them apart at the appropriate places so that the various virus proteins in the cell can assemble into new viruses. Now that we know the structure of this protease, scientists around the world can specifically look for active substances that block this protease. Such protease inhibitors have proven to be excellent medications for many viral diseases – especially HIV.
When can you expect a suitable active ingredient?
One will first try to fight the new coronavirus with already known drugs or with a combination of known drugs. The development of a completely new active ingredient can easily take over ten years. But it should go much faster if corona is now working together intensively worldwide and perhaps the regulatory hurdles are also eased somewhat. We will see what we can do in the light of current developments. Our accelerator center will now be closed. But if research groups want to do corona virus experiments, we can start up the accelerator again within a day.
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