COVID-19: the virus blocks cellular defenses
COVID-19 blocks the production of protective proteins
Now, a multidisciplinary team of Yale researchers has discovered how SARS-CoV-2, the virus that causes COVID-19, accomplishes this trick by blocking the production of cellular proteins, including immune molecules, and contributes to severe disease in its host.
"The virus essentially reprograms host cells, and by understanding this mechanism, we can hope to develop new therapies," said Yong Xiong, Professor of Molecular Biophysics and Biochemistry.
Previous studies had implicated a viral protein, the non-structural protein 1 or Nsp1, in COVID-19's ability to block the cells' ability to produce new proteins. But it was not clear how NsP1 functioned in a cell.
Using advanced genetic screening and cryo-EM, the Yale team was able to show that Nsp1 is one of the most pathogenic viral proteins in COVID-19. In human lung cells, it can radically alter the host cell's gene expression and essentially form a plug that prevents the ribosome - the cell's protein-making machine - from receiving genetic instructions for new proteins encoded in messenger RNA.
A mechanism blocked by Nsp1
The SARS-CoV-2 protein Nsp1 plugs the messenger RNA (mRNA, the genetic blueprint) entry channel on the ribosome to block the production of the host protein. "This is the entry channel for genetic material, and when it is blocked, no protein can be made," Xiong explained. "We didn't understand this mechanism before, but now we do. »
This process affects protein production in many parts of the body, and high levels of SP1 may help explain why some people get seriously ill after being infected with COVID-19, he said.
However, it is still not known how the virus is able to produce its own proteins, using the same ribosome, to replicate in the cell after disabling the cells' ability to make normal proteins, Xiong said. But most importantly, by better understanding this virus, researchers will be better equipped to produce more effective vaccines or drugs.
Translated with www.DeepL.com/Translator (free version)
