Researchers identify a protein that can help SARS-CoV-2 spread rapidly through cells

Eric Ross and Sean Cascarina, biochemistry and molecular biology researchers at Colorado State University, have released a research paper identifying a protein encoded by SARS-CoV-2, the virus that causes COVID-19, which can be associated with the rapid spread of the virus through cells in the human body.

Through vigorous application of the fundamental sciences and bioinformatics analysis, her research highlights important characteristics of the virus that could one day be important in the development of a treatment for COVID-19.

Before COVID-19 studied Ross and Cascarina prions – shortened proteins that can transfer their abnormal form to normal variants of the same protein. Prions cause several fatal and transmissible neurodegenerative diseases, including Mad Cow Disease in cattle and Creutzfeldt-Jakob disease in humans. Cascarina’s sub-focus has been on low complexity domains – regions in the sequence of a protein that differ from typical regions in their amino acid composition and chemical behavior.

What makes these low-complexity protein domains interesting is their tendency to separate liquid-liquid phase, similar to oil separation of water. Some of these proteins form “biomolecular condensates” in a cell, which are small areas in a cell where the protein is highly concentrated, analogous to the oil droplets that form when oil separates from water.

Create new virus packages

When Ross and Cascarina pivoted to study COVID-19 earlier this year, they found that the nucleocapsid, as N, protein in the SARS-CoV-2 virus has a low-complexity domain that separates fluid-liquid. can be used to facilitate the packaging of viral RNA into new virus particles that can infect neighboring cells.

The N protein may also be associated with reducing an anti-viral stress response of an infected cell. Cells often form something called stress granules, a type of biomolecular condensate, to respond to a change in their environment, and these granules can have an anti-viral effect.

“The cell can respond to a stressful event by making changes in the cellular environment,” Ross said, “including making these modifications to some proteins.”

“But viruses obviously want to prevent cell defense,” Cascarina added. “They want to be infected so they can sometimes regulate these stress granules.” By suppressing the normal stress response, the virus can reduce the anti-viral responsiveness of the cell.

Since accepting their paper on May 31, four other labs across the country have confirmed parts of Cascarina’s hypothesis about the N protein.

The application of this research may be for the development of treatments if one person has already contracted the virus, instead of preventing infection such as a vaccine. Both of these research areas are essential to slow down and end the COVID-19 pandemic.

“Medically, if you can counteract the ability of the virus with the immune response of a cell, then you could help the cells fight the virus,” Ross said. “I think this falls into the category of very basic science: if we understand the viral process, then we can conceivably try to design a drug that reverses that process.”