Mutated coronavirus binds up to seven times stronger to receptor

The “South African variant” binds three times as hard

Mutations in the coronavirus spike protein bind up to seven times stronger receptor in our body cells. Erasmus MC researchers discovered it after analyzing the coronavirus variants that were first described in England and South Africa. The strong binding can contribute to the faster propagation of these variants.

The variant of the coronavirus that was identified in England, also commonly known as the British variant, binds seven times more strongly to the so-called ACE2 receptor on cells of the human body than the original variant of the Wuhan virus. The “South African variant” binds three times as hard. This is the conclusion of researchers from the Department of Molecular Genetics headed by biochemist Dr Joyce Lebbink in the scientific journal Journal of Molecular Biology .

Single atoms
A bond that is seven times stronger is a big difference, says Lebbink. “You have to understand that this is an altered amino acid between the original variant and the England variant. We’re only talking about a few atoms that make such a big difference.

The stronger binding may contribute to the faster spread of coronavirus mutants, she says. “The binding of the virus to the cells of the body is not the only factor that determines infectivity, but from a biochemical point of view, this correlation does not surprise us. These viral variants bind to the receptor longer than the original virus and are therefore more likely to enter the cell. ‘

Flowing on the chip
The research involved a sample of genetic and technological ingenuity. Using synthetic DNA, the researchers mimicked pieces of the spike protein from variants of the coronavirus and the human ACE2 receptor to which the virus binds. By sinking the pieces of spike protein in a liquid on a chip with a layer of ACE2 receptors, scientists were able to determine how quickly the spike protein binds to the receptor and how quickly it releases again. Combined, this determines the affinity, or strength of the bond. By repeating the experiment with the different viral variants, the researchers came to a comparison.

DNA repair
Lebbink and his colleagues Charlie Laffeber, Kelly de Koning and Professor Roland Kanaar are normally working on DNA repair. A completely different area of ​​coronaviruses. “It’s a journey, started during the first containment. Like many other scientists, we wanted to contribute something,” says Lebbink. The technique they use to measure, for example, how mutated proteins bind to l DNA, has been shown to be equally applicable for the interaction between the coronavirus and the ACE2 receptor. In the meantime, normal work has largely resumed, but it is also planned to determine the binding of the problematic variant in India. .