When the coronavirus causing COVID-19 infects human cells, the cell’s protein-processing machinery makes modifications to the spike protein that render it more flexible and mobile, which could increase its ability to infect other cells and to evade antibodies, a new study from the University of Illinois Urbana-Champaign found.
The researchers created an atomic-level computational model of the spike protein and ran multiple simulations to examine the protein’s dynamics and how the cell’s modifications affected those dynamics. This is the first study to present such a detailed picture of the protein that plays a key role in COVID-19 infection and immunity, the researchers said.
Biochemistry professor Emad Tajkhorshid, postdoctoral researcher Karan Kapoor and graduate student Tianle Chen published their findings in the Proceedings of the National Academy of Sciences.
“The dynamics of a spike are very important — how much it moves and how flexible it is to search for and bind to receptors on the host cell,” said Tajkhorshid, who also is a member of the Beckman Institute for Advanced Science and Technology. “In order to have a realistic representation, you have to look at the protein at the atomic level. We hope that the results of our simulations can be used for developing new treatments. Instead of using one static structure of the protein to search for drug-binding pockets, we want to reproduce its movements and use all of the relevant shapes it adopts to provide a more complete platform for screening drug candidates instead of just one structure.”
The spike protein of SARS-CoV-2, the virus that causes COVID-19, is the protein that juts out from the surface of the virus and binds to receptors on the surface of human cells to infect them. It also is the target of antibodies in those who have been vaccinated or recovered from infection.
Many studies have looked at the spike protein and its amino acid sequence, but knowledge of its structure has largely relied on static images, Tajkhorshid said. The atomistic simulations give researchers a glimpse of dynamics that affect how the protein interacts with receptors on cells it seeks to infect and with antibodies that seek to bind to it.
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