Computer simulations have shown that mutations in the SARS-CoV-2 spike protein, which enhance the virus’s ability to bind to the ACE2 receptor, occur in two clusters or “hot spots” of mutations.
SARS-CoV-2 evolved to acquire mutations in a spike protein, the part of the virus that protrudes from its surface and clings to cells for infection. Mutations in this part of the coronavirus increase its ability to bind to human cells or evade antibodies. A new study by the Centers for Genomics and Systems Biology at New York University and New York University in Abu Dhabi uses computer simulations to assess the biological significance of spike protein mutations. The goal is to identify versions of the virus that bind more strongly to the ACE2 receptor or more actively resist antibodies.
Scientists suggest that it is these mutations in the spike protein that are the key reason for the rapid spread of the virus in some parts of the world.
In recent months, new and more infectious strains of the coronavirus have emerged, leading to new waves of the epidemic in countries such as India and Brazil. The worsening situation requires methods for the rapid prediction of new infectious viral strains. But keeping track of new options is not an easy task; genome sequencing shows that the SARS-CoV-2 spike protein alone, for example, has about 5,000 possible variants.
Screening such a wide range of options poses a huge challenge for traditional experimental methods, the researchers note. The advantage of computer simulations is that one hundred mutations can be easily estimated in a few days.
The scientists turned to a computational technique that models how the SARS-CoV-2 spike protein recognizes the ACE2 receptor – a protein on the surface of many types of cells – to enter host cells. They evaluated 1,003 combinations of mutations in the coronavirus spike proteins, including those that have led to a spike in infections in Brazil, South Africa, the UK and India.
A systematic evaluation of the variants showed that spike mutations that strongly bind to the ACE2 receptor occur in two clusters or “hot spots” of mutations at the binding interface. They are located in structurally flexible regions. This means that mutations that increase binding have effectively reprogrammed the spine conformation to enhance its ability to recognize ACE2 receptors.
The study is published in the Journal of Molecular Biology.