COVID-19: How the virus shuts down our protein synthesis, causing the immune system to completely collapse.

Researchers from Munich and Ulm, Germany, have identified how the pandemic coronavirus SARS-CoV-2 inhibits the synthesis of proteins in infected cells and has shown that it effectively relieves the body’s inherent immune system. Non-structural protein 1 (Nsp1), encoded by the coronavirus SARS-Cov-2, has now been shown to have devastating effects on host cells.

COVID-19: How the virus shuts down our protein synthesis, causing the immune system to completely collapse.

Nsp1 is actually one of the core weapons that viruses use to ensure that they replicate and spread in the human host. Nearly 20 years ago, nsp1 was identified as a toxicity factor after the SARS coronavirus outbreak, which was shown to inhibit protein synthesis in infected cells. Now, researchers at Ludwig-Maximilian University (LMU) and Ulm University Hospital in Munich have confirmed why Nsp1 is so effective in COVID-19. In a paper in the journal Science, the way this protein works is described in detail.

In all biological cells, the task of synthesizing proteins is done by complex molecular machines of ribosomes. Ribosomes interact with messenger RNA, which is the blueprint for protein synthesis and converts each messenger RNA sequence into an amino acid sequence of the corresponding protein. The amino acid sequence in turn determines the shape and biological function of each protein. The ribosome consists of two different subbases, Nsp1 combined with a smaller 40S subkey. MRNA initially binds to the small sub-subkey, which then interacts with 60S subkeys to form a cavity, and then mRNA passes through it. New research shows that one end of the Nsp1 protein interacts with 40S subunits, preventing mRNA binding.

With high-resolution cryogenic electron microscopes, Professor Roland Beckmann of the LMU Gene Center and his colleagues have shown in detail in 3D space how Nsp1 binds tightly to specific pockets in the small ribosome sub-base and inhibits the formation of functional ribosomes. Further experiments have shown that Nsp1 can also interact with a specific configuration state of a fully assembled ribosome.

In addition, a team led by Konstantin Sparrer of Ulm University Hospital was able to demonstrate that the cessation of protein synthesis led to a near-total collapse of one of the body’s main lines of defense against the virus. Nsp1 inactivates the innate immune response by inhibiting an important signal cascade. The study’s authors hope that the insights gained will have the potential to find ways to neutralize the new coronavirus, thereby reducing the severity of respiratory diseases it causes. One potential way, they say, is to develop a molecule to mask the binding sites of viral proteins. This should be feasible because the Nsp1 binding bag itself does not seem to play an important role in the ribosome function.

Original search: Rh basis for translational and iad i a’ sion y sienn by the Nsp1 protein of SARS-CoV-2.

(Biocom: Woodson)