Like a pirate hijacking a ship, a virus takes control of an infected cell because every virus depends on the resources and molecular machines of the cell to multiply. This also applies to SARS-CoV-2, the causative agent of the COVID-19 pandemic. Researchers at ETH Zurich and the University of Bern have now discovered a mechanism that the corona virus uses to favor the production of its proteins over the cell's own ones. This mechanism leads to the cells greatly reducing the production of their own proteins, and instead producing almost only viral proteins. This not only boosts the production of new viruses, but also inhibits the immune response against the corona infection.
After the virus has entered a human cell during a SARS-CoV-2 infection, the viral protein NSP1 is produced as one of the first viral proteins. It was already known from other corona viruses that NSP1 inhibits the production of the cell's own proteins, but it was not yet clear how this occurs. The collaborating groups from ETH Zurich and the University of Bern have now discovered how NSP1 inhibits cellular protein production. This work now appears in press and complements the independently obtained results on a related topic that were recently published by a research team in Germany.
A starting point for vaccine and drug development
Ribosomes are the cellular machines that produce proteins. They read the blueprint, the so-called messenger RNA, for a given protein and assemble the amino acids in the corresponding order. During reading, the messenger RNA passes through a channel on the ribosome. The researchers could show that NSP1 binds to this channel and thus blocks the ribosome. Using cryo-electron microscopy, the binding site of NSP1 in the ribosome channel could be elucidated 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. If NSP1 can no longer interact with the ribosome, this allows activation of cellular defense systems that can stop viral replication," explains Nenad Ban, Professor for Molecular Biology at ETH Zurich and co-author of the study.