3D Geometry of SARS Cov2 – Mapping Coronavirus genome
The SARS-CoV-2 virus uses the structures within its RNA to invade cells. With the identification of these configurations, scientists have now generated the most comprehensive atlas in the form of 3D geometry of the SARS-CoV2 genome.
The most relevant map of these genomic structures to date has been made by a team led by an RNA scientist Anna Marie Pyle. She posted two preprints of mapped structures of the entire RNA genome of the Corona Virus SARS-CoV-2 in July 2020 to bioRxiv.org. They used both living cells and computational analysis for the same.
The new Coronavirus’s genome is contained in a long noodle-like molecule, but it does not look like cooked noodles, but it folds into different shapes like coils, stems, and clover-leaf. These structural variations evoke molecular origami in the RNA.
SARS-CoV-2 owing to its unique RNA structure, infects people and causes the COVID-19 illness. The contributions of the different structures taken up the virus RNA is often underappreciated, even by the scientists, says Pyle, a Howard Hughes Medical Institute Investigator, Yale University.
Pyle stated that the general wisdom is that if the proteins encoded in the virus’s genome is known, then the functioning of the virus can be understood. For the SARS CoV 2 Virus, the structure of the RNA in the genome can influence their ability to function as much as the encoded proteins.
Researchers can start to detangle the mystery behind these structures helping the virus and reveal information that could lead to the discovery of new treatments for COVID-19. Like for instance, once the key structure involved in the infection is identified, it may be possible to disrupt the networks and interfere with the infection. But structuring the 3-D geometry of SARS-CoV-2 can be tricky.
More bang for the buck
DNA and RNA both code their information in four letters. The DNA forms bonds that span along the two strands of DNA. These strands twist together and form a familiar double helix. RNA can form helices too, but in SARS-CoV-2, the double helix forms when a single strand folds back on itself rather than two strands like in the DNA double helix.
The size of SARS-CoV-2’s genome is about 30,000 RNA letters. The limited number of the gene in the RNA is compensated by the 3- dimensional structures formed by the RNA with the contortion of its unusually long RNA. Dr. Pyle asserted that an RNA virus gets the most bang for its buck, depending on how it uses its genome.
Research on other viruses has provided insights on how viruses use their RNA structures to do the dirty work. For example, according to Jeffrey Kieft, the hepatitis C virus forms a complex configuration of RNA to manipulate host cells into making viral protein. Dr. Kieft is an RNA virologist and structural biologist at the University of Colorado Anschutz Medical Campus. He says that It is incredible how the RNA structures apply different approaches during viral infections.
Capturing the Image of SARS CoV2 RNA in live cells.
Pyle’s team deciphered the configuration of SARS-CoV-2’s genome with two approaches. In one study, they studied the structure of the RNA from within the virus’s natural environment, i.e., the infected host cells. Another study was carried out through computational methods.
Viral RNA is difficult to access within the infected cells as the viral RNA mixes with that of the host genome. However, in SARS-CoV-2 infection, the RNA quantity becomes unusually abundant in the host cell. This helped the team to create a picture of the full structure of the RNA genome. This was the first time a comprehensive image of a viral genome in living cells was captured.
Simultaneously, the team tried to predict how SARS-CoV-2’s RNA genome, along with the other structures of viral RNA made by the cell, might fold and interact with each other.
These studies have not undergone peer review yet, but together, these two processes reveal the complex and compact architecture of SARS-CoV-2’s genome. Pyle also mentions that the pandemic virus genome has more structure than any RNA her lab previously studied.
To study any RNA virus, and SARS-CoV-2 in particular, a direction guide of its genomic landscape is required. Dr. Kieft commented in a statement that Dr. Pyle had created a likely roadmap that would be a great start point for the subsequent better targeted and specific experiments. He also states Dr. Pyle’s work, in many ways, gives an overview of the richness of RNA structure that is likely to exist in this virus.
The mapping effort represents a preliminary fit towards new drugs targetting the RNA structure of the virus. However, this could be a long process. As early as 2014, Dr. Keift has been working on viruses like Dengue and West Nile. He has been working on neutralizing knot-like structure viruses use to evade host cellular defense.
Kieft mentions that the research community is not entirely equipped to identify RNA structure disrupting drugs. The role of RNA structure has not been studied or pursued in the way it has for proteins Dr. Kieft mentions. However, when it comes to a pandemic virus, the SARS-CoV-2, initially, it is likely to try everything that might work he mentions.
3D Geometry of SARS Cov2