A group of researchers from Vir Biotechnology, California and the MRC-University of Glasgow Centre for Virus Research claimed that viruses carrying N439K variant show more virulence compared to British B.1.1.7 variant, and South African variant B.1.351
Although the British variant, called B.1.1.7, and the South African, B.1.351, have received more attention, the N439K variant is the second most common in the receptor-binding domain (RBD), that is, the immunogenetic fragment of a virus that enters the host’s cells. It was first detected in Scotland in March 2020 and since then a second lineage (B.1.258) has emerged independently across Europe, present in more than 30 countries around the world in January 2021.
Now, a group of researchers from the MRC-University of Glasgow Center for Virus Research has claimed that viruses carrying this mutation show more virulence in their ability to spread, so they can bind to the receiver more strongly.
According to a peer-reviewed study published in the journal ‘Cell’, an international team of scientists has characterized the effect and molecular mechanisms of an amino acid change in the spike protein of SARS-CoV-2’s N439K and discovered that this mutation confers more resistance to serum antibodies in some people.
“This means that the virus has many ways to alter the immunodominant domain to evade immunity while retaining the ability to infect and cause disease,” said lead author Gyorgy Snell, director of biology at Vir Biotechnology.
“A significant finding from this paper is the extent of variability found in the immunodominant receptor binding motif (RBM) on the spike protein.”
The report also shows the X-ray crystal structure of N439K and Snell explains that “this analysis shows that the new mutation introduces an additional interaction between the virus and the ACE2 receptor.”
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“A single amino acid change (asparagine to lysine) enables the formation of a new point of contact with the ACE2 receptor, in line with the measured two-fold increase in binding affinity. Therefore, the mutation both improves interaction with the viral receptor ACE2 and evades antibody-mediated immunity,” he continues.
Once the researchers determined that this variant did not change the replication of the virus, they studied whether it allowed the evasion of antibody-mediated immunity by analyzing the binding of more than 440 polyclonal serum samples and more than 140 monoclonal antibodies from recovered patients. Thus, they have found that the binding of a proportion of monoclonal antibodies and serum samples was significantly decreased with N439K.
Snell notes that one of the challenges in studying SARS-CoV-2 variants is the limited amount of sequencing currently being done overall, with more than 90 million cases of covid-19 being recorded and only about 350,000 variants of the virus have been sequenced.
“That’s only 0.4%–just the tip of the iceberg,” he says, adding that it highlights “This underscores the need for broad surveillance, a detailed understanding of the molecular mechanisms of the mutations, and for the development of therapies with a high barrier to resistance against variants circulating today and those that will emerge in the future”.
