Discovery of shape of the SARS-CoV-2 genome after infection could inform new COVID-19 treatments


06-11-2020
  Coronavirus  Credit: Pete Linforth on Pixabay

Scientists at the University of Cambridge, in collaboration with Justus-Liebig University, Germany, have uncovered how the genome of SARS-CoV-2 - the coronavirus that causes COVID-19 - uses genome origami to infect and replicate successfully inside host cells. This could inform the development of effective drugs that target specific parts of the virus genome, in the fight against COVID-19.

SARS-CoV-2 is one of many coronaviruses. All share the characteristic of having the largest single-stranded RNA genome in nature. This genome contains all the genetic code the virus needs to produce proteins, evade the immune system and replicate inside the human body. Much of that information is contained in the 3D structure adopted by this RNA genome when it infects cells.  

The researchers say most current work to find drugs and vaccines for COVID-19 is focused on targeting the proteins of the virus. Because the shape of the RNA molecule is critical to its function, targeting the RNA directly with drugs to disrupt its structure would block the lifecycle and stop the virus replicating.

In a study published in the journal Molecular Cell, the team uncovered the entire structure of the SARS-CoV-2 genome inside the host cell, revealing a network of RNA-RNA interactions spanning very long sections of the genome. Different functional parts along the genome need to work together despite the great distance between them, and the new structural data shows how this is accomplished to enable the coronavirus life cycle and cause disease.

“The RNA genome of coronaviruses is about three times bigger than an average viral RNA genome – it’s huge,” said lead author Dr Omer Ziv at the University of Cambridge’s Wellcome Trust/Cancer Research UK Gurdon Institute.

He added: “Researchers previously proposed that long-distance interactions along coronavirus genomes are critical for their replication and for producing the viral proteins, but until recently we didn’t have the right tools to map these interactions in full. Now that we understand this network of connectivity, we can start designing ways to target it effectively with therapeutics.”

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Image: Coronavirus

Credit: Pete Linforth on Pixabay

 

The University of Cambridge is acknowledged as one of the world's leading higher education and research institutions. The University was instrumental in the formation of the Cambridge Network and its Vice- Chancellor, Professor Stephen Toope, is also the President of the Cambridge Network.

University of Cambridge (cam.ac.uk)