November 29 December 5 2021
The N501Y mutation enhances the transmissibility of variants
Coronaviruses contain an RNA genome. The enzymes involved in their replication make more errors than those in DNA viruses. For this reason, the more an RNA virus spreads, i.e. multiplies, the more likely it is that variants will emerge. The mutations that have the greatest effect on the virus are those in the spike (S) surface protein. This protein combines with the ACE2 cellular receptor to facilitate the entry of the virus into the cell, and is the principal target of antibodies. A more highly transmissible variant emerged at the beginning of the summer of 2020, the Alpha (UK) variant. Researchers at the University of Texas at Galveston have investigated which mutation or combination of mutations was responsible for this increased transmissibility.
The Alpha variant carries 8 mutations in the S protein, and one deletion, that is, the loss of a tiny part of its genome (corresponding to 2 amino acids). The researchers firstly evaluated the impact of each of the 8 mutations and of the deletion in the spike protein by constructing viruses that each possessed only one of these differences. They inoculated hamsters, the animal model used for COVID-19 research. The conclusion was that only the viruses with either the deletion or the mutation N501Y possessed increased transmissibility. The same test was carried out in vitro, using cell culture testing, on cells from human respiratory passages, and also showed that the N501Y mutation had an advantage regarding transmission in the upper respiratory airways.
However, the spike protein with all 8 mutations has even higher transmissibility than the one with only the N501Y mutation. The scientists therefore concluded that the N501Y mutation was the major mutation in enabling the Alpha variant to have high transmissibility, but not the only one.
This mutation also emerged in other variants, such as the Beta (South African) and the Gamma (Brazilian). It became dominant at the beginning of 2021 in circulating variants.