A research team has uncovered how the genome for SARS-CoV-2, the virus responsible for COVID-19, uses a "genome origami" strategy in infecting human host cells and replicating inside it.

Scientists from the University of Cambridge in the United Kingdom, together with scientists from Justus-Liebig University in Germany have worked in understanding this replication mechanism in this particular strand of coronavirus. This family of viruses contains some of the largest single-stranded RNA genomes ever found in nature.

A virus' genome contains the genetic codes that define a virus, as well as the information it needs to synthesize its proteins - including those that allow it to bypass the host's immune response and bond with the target cells, replicating soon after.

With this new discovery, researchers hope to better inform future efforts to develop drugs designed to combat certain parts of the virus genome to deactivate it or restrict its harmful effects on the human body.

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Mapping The Entire Viral Structure

The team detailed the entire interactome, or all molecular interactions relating to, the SARS-Cov-2, in a report published in the journal Molecular Cell on Thursday, November 5. This includes both short- and long-range RNA-RNA interactions, some which involve the longer sections of the coronavirus genome. Considering its relatively large genome, that COVID-19 causing virus requires communication between its distant functional groups, and this collaborative effort between Cambridge and Justus-Liebig details these mechanisms - illustrating the life cycle of the virus and its infection mechanism.

"The RNA genome of coronaviruses is about three times bigger than an average viral RNA genome-it's huge," shared Dr. Omer Ziv, lead author of the study from the Wellcome Trust/ Cancer Research UK Gurdon Institute at the University of Cambridge, in an article from the University. Dr. Ziv additionally explained that previous studies suggested that long-distance interactions are important components of the virus' replication, but lacked the full access 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," Dr. Ziv added.


Detecting a Ribosomal Stop-and-Go

For cells, the production of certain proteins is based on the data stored in the genome. These proteins are synthesized after ribosomes - a macromolecular machine itself made of RNA and proteins - runs along with the virus' RNA, going through the genetic code until it reaches a termination code. In coronaviruses, however, there is a specific spot where ribosomes are terminated only 50 percent of the time. For the other half of the time, a unique shape allows the ribosome to bypass the "stop sign," producing additional viral proteins.

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"We show that interactions occur between sections of the SARS-CoV-2 RNA that are very long distances apart, and we can monitor these interactions as they occur during early SARS-CoV-2 replication," added Dr. Lyudmila Shalamova, co-lead investigator in the study from Justus-Liebig University.

Dr. Jon Price, co-lead in the study and a postdoc associate at the Gurdon Institute, developed an open-access interactive website containing the entire mapping of the RNA structure for SARS-Cov-2, allowing researchers to use this information for future studies regarding the virus.

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