Researchers at the Swiss Federal Institute of Technology in Zurich (ETH) and the University of Bern have made a breakthrough in their investigations into the coronavirus. They have discovered how the virus manipulates human cells in order to guarantee its own replication. This mechanism leads to a situation in which cells begin to primarily produce virus proteins rather than their own proteins. This stimulates the production of new viruses on the one hand, while on the other, the body’s immune response against the infection is also inhibited.
In a coronavirus infection, the virus protein NSP1 is initially produced, as detailed by an article published by ETH. It was also previously known that NSP1 inhibits the production of cell proteins. The Swiss research group has, however, now also discovered exactly how this process happens. According to the research, NSP1 binds to a channel after passing through this on a ribosome, thereby blocking the progression of the ribosome. Under normal circumstances, the messenger RNA passes through this channel, allowing the ribosome to read off the blueprint for the production of proteins.
Using cryo-electron microscopy, the researchers were able to display the binding site of NSP1 in the ribosome channel at atomic resolution. “This detailed image provides important information for potential design of a drug that can prevent NSP1 binding without interfering with ribosomal function” explains Nenad Ban, Professor for Molecular Biology at ETH Zurich, before adding: “If NSP1 can no longer interact with the ribosome, this allows activation of cellular defense systems that can stop viral replication”.
Among other achievements, the research group has also been able to successfully produce modified NSP1 variants that have lost their inhibitory effect. These kinds of attenuated, inactive viruses could potentially be used as the basis of a vaccine, according to information in the press release.
According to the ETH, the research project has been completed in record time. “The complementary expertise of the researchers involved allowed for very fast and efficient progress in this project," says Oliver Mühlemann, Professor of Biochemistry at the University of Bern. The researchers intend to continue collaborating closely with the aim of gaining further knowledge about the manipulation of cells by the coronavirus.