Scientists find how Sars-CoV-2 shutdown protein synthesis

Hyperaxion Jul 22, 2020

In a new study, researchers found how the new coronavirus inhibits one of the most important cellular processes in our body.

Researchers from Munich and Ulm, Germany, have determined how Sars-CoV-2 inhibits protein synthesis in infected cells. In an article published last week in the journal Science, they explain that the new coronavirus effectively “disarm” the body’s innate immune system.

Scientists find how Sars-CoV-2 shutdown protein synthesis
(Credit: Science).

As the scientists explain, the Nonstructural Protein 1 (Nsp1) encoded by Sars-Cov-2 is one of the main instruments used by the virus to guarantee its replication and propagation in human hosts.

Nsp1 was initially identified during the SARS outbreak, caused by another type of coronavirus, between 2002 and 2003 in China.

In all biological cells, the task of synthesizing proteins is performed by complex molecular machines called ribosomes, structures that interact with messenger RNAs (mRNAs), which serve as a model for protein synthesis.

These organelles allow mRNA components to be “translated” into amino-acids, forming new proteins. The amino-acid sequence, in turn, determines the shape and biological function of each individual protein.

In addition, ribosomes are formed by two distinct subunits known as 40S subunit (the smaller one) and 60S subunit. The mRNA binds to the small subunit before interacting with the large one, forming a cavity that will allow amino-acid synthesis.

In the new study, however, scientists show that Sars-Cov-2’s Nsp1 affects the 40s subunit, preventing it from binding to the mRNA and thus disrupting this cellular process.

According to the scientists, this is because Nsp1 binds so tightly to a part of the 40s subunit that it ends up inhibiting the formation of functional ribosomes.

The research also revealed that Nsp1 can interact with fully formed organelles.

As the article explains, inhibiting protein translation has a direct impact on the immune system, as it disables one of the body’s most important processes. “Nsp1 effectively blocks innate immune responses that would otherwise facilitate clearance of the infection,” the researchers wrote.

For the team, the discovery is a step forward in the search for ways to neutralize the new coronavirus. For them, a potential approach would be to develop a molecule that “masks” the location to which the Nsp1 protein binds.

“The structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2,” they wrote in the article.

Related topics:

Coronavirus Covid-19

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