Scientists at Cambridge University, in collaboration with Justus-Liebig University, Germany, have discovered how the genome of SARS-CoV-2 ̵1; the coronavirus that causes COVID-19 – uses the genome origami to spread the virus. It infects and replicates successfully inside the host cell. 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 the many coronaviruses. They all share the same feature of having the largest single-stranded RNA genome in nature. This genome contains all the genetic codes a virus needs to make proteins, evade the immune system, and replicate inside the human body. Much of that information is contained in the 3-D structure used by this RNA genome when it infects cells.
Most of the current work to find drugs and vaccines for COVID-19 has been focused on targeting viral proteins, the researchers said. Because the shape of the RNA molecule is so important to its function, targeting RNA directly with drugs to disrupt its structure suppresses its lifecycle and prevents viral replication. .
In a study published today in the journal Molecular cellsThe team discovered the entire structure of the SARS-CoV-2 genome inside the host cell, revealing a network of RNA-RNA interactions that span very long parts of the genome. The different functional parts along the genome need to work together despite the very long distances between them and the new structural data that shows how this is done to activate the coronavirus’s life cycle and cause disease.
“The coronavirus RNA genome is about three times larger than that of the average virus – it’s huge,” said lead author, Dr Omer Ziv at the Wellcome Trust Cancer Research Institute / University of Cambridge, UK. , said.
Researchers previously suggested that long-distance interactions along the coronavirus genome were critical for their replication and production of viral proteins, but until recently they I don’t yet have the right tools to fully map these interactions. network connections, we can start to design ways to target it effectively with therapy. “
In all cells, the genome holds the code for the production of specific proteins, produced when a molecular machine called the ribosome runs along the RNA reading the code until there is a ‘stop sign’ indicating it is finished. . In coronavirus, a special feature is that the ribosome only stops 50% of the time before the stop sign. In another 50% of cases, a single RNA shape causes the ribosome to jump over the stop marker and produce additional viral proteins. By mapping this RNA structure and related long-range interactions, the new study uncovered strategies by which coronaviruses produce their proteins to manipulate our cells.
Dr. Lyudmila Shalamova, an associate, said: “We show that interactions occur between parts of the SARS-CoV-2 RNA that are very far apart and we are able to track these interactions as they occur. during early transcription of SARS-CoV-2. Investigator at Justus-Liebig University, Germany.
Dr. Jon Price, a postdoctoral associate at the Gurdon Institute and co-lead of the study, has developed a free, open-access interactive website that hosts the entire RNA structure of SARS-CoV-2. This would allow researchers around the world to use new data in drug development to target specific regions in the viral RNA genome.
The genome of most human viruses is made of RNA, not DNA. Ziv has developed methods to investigate such long-range interactions between viral RNA genomes within the host cell, in order to understand the Zika virus genome. This demonstrates a valuable methodological basis for understanding SARS-CoV-2.
The virus that caused COVID-19 puts a cell protection vulnerability
Omer Ziv et al., Short and long-range RNA-RNA interactions of SARS-CoV-2, Molecular cells (Year 2020). DOI: 10.1016 / j.molcel.2020.11.004
Provided by Cambridge University
Quote: SARS-CoV-2 uses ‘genome origami’ to infect and replicate inside the host cell (2020, November 5) retrieved November 6, 2020 from https://phys.org/news / 2020-11-sars-cov-genome-origami -infect-replicate.html
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