University of Alberta research shows how cell membranes play a much bigger role than previously understood in allowing spike proteins on viruses to infect cells. The findings, published in the journal iScience, could give scientists top of the submit tackling SARS-CoV-2the virus that triggers COVID-19along with other potentially deadly viruses.
The team of researchers, led by U of A professor of biochemistry Michael Overduin, used software called Membrane Optimal Docking Area (MODA) to recognize interactions between proteins and membranes within cells.
Once the COVID-19 pandemic turn off labs at the U of A, Troy Kervin, an undergraduate student in Overduin’s lab, shifted his research to work he could do outside the lab. He assembled all of the proteins in a single category of membrane-binding domains, and used MODA to predict which regions on the domains bind to membranes. He discovered that cell membranesthe barrier around cells manufactured from molecules called lipidsplay a far more significant role in viruses binding to cells than previously thought.
Those findings became the building blocks for additional research about cell-binding activity, namely if spike proteinssuch as for example those on the SARS-CoV-2 virusbind to membranes.
The consensus in the scientific community has been that the work of spike proteins in SARS-CoV-2 would be to bind to angiotensin converting enzyme-2 (ACE-2) receptors which are externally of cells, never to the cell membrane.
By using another undergraduate student, Anh Tran, the team began the procedure of using MODA to compare a lot of structures of spike proteins in both originalor ‘wild type’virus and the variants.
“We discovered the way the spike protein engages the lipids of our lung cells and gets in. Then we discovered that the Omicron variant was super active. We thought that’s really, really exciting. Maybe that’s adding to how it gets in easier and spreads quicker,” says Overduin.
The team thinks that other viruses apart from SARS-CoV-2 use similar mechanisms to enter cells, but until recently the procedure has been difficult to see. The development of software like MODA helps it be better to make predictions such as this and describe how proteins really behave in a cell. “We’re at the start of the digital age where we are able to really see a lot more than we’re able to see even 2 yrs ago, where we are able to look at every protein in the human genome and measure how everyone could connect to membranes,” says Overduin.
More info: Michael Overduin et al, Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins, iScience (2022). DOI: 10.1016/j.isci.2022.104722
Citation: Cell membranes play a more substantial role than thought in allowing spike proteins on viruses to infect cells (2022, September 16) retrieved 18 September 2022 from https://medicalxpress.com/news/2022-09-cell-membranes-larger-role-thought.html
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