A corona virus keeps the world in suspense. SARS-CoV-2 is highly contagious and can cause severe pneumonia with shortness of breath (COVID-19). Medical research worldwide is looking for ways to prevent the proliferation of viruses with the help of medication. A team from the University of Lübeck has found a promising approach. Using the high-intensity X-ray light from the Berlin synchrotron source BESSY II, they have deciphered the three-dimensional architecture of the main viral protease of SARS-CoV-2. The main viral protease is involved in the multiplication of the virus.
Teams worldwide are researching the development of active substances against SARS-CoV-2. The structural analysis of macromolecules that perform a function in the virus is important for this. This function is closely related to the three-dimensional architecture of the macromolecule. If you know this three-dimensional architecture, you can specifically identify targets for active ingredients.
Stop the virus from multiplying
A special protein is involved in the multiplication of viruses: the viral main protease (M pro or 3CL pro ). Now a team led by Prof. Dr. Rolf Hilgenfeld, University of Lübeck, decoded the three-dimensional architecture of the main protease of SARS-CoV-2. The researchers used the high-intensity X-ray light from the BESSY II system at the Helmholtz-Zentrum Berlin.
Fast track access to BESSY II
“We enable fast-track access to our instruments especially for such highly topical issues,” says Dr. Manfred Weiss, who heads the macromolecular crystallography group at HZB. On the so-called MX instruments, which the group looks after, tiny protein crystals can be illuminated with highly brilliant X-rays. The images contain information about the three-dimensional architecture of the protein molecules. The complex shape of the protein molecule and its electron density can be calculated with the help of computer programs.
Results help in drug development
This now gives concrete starting points for developing active ingredients. These could specifically target weak points in the macromolecule and hinder its function. Rolf Hilgenfeld is a globally recognized expert in the field of virology and developed an inhibitor against this type of virus during the SARS pandemic in 2002/2003. In 2016, he succeeded in decoding an enzyme from the Zika virus.
Publication: Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Linlin Zhang , Daizong Lin, Xinyuanyuan Sun, Ute Curth, Christian Drosten , Lucie Sauerhering , Stephan Becker , Katharina Rox , Rolf Hilgenfeld