The UK COVID-19 Variant Has Mutated... Again

Colorized scanning electron micrograph of an apoptotic cell (red) heavily infected with SARS-CoV-2 virus particles (yellow), isolated from a patient sample. Image credit: NIH Image Gallery/Flickr (Public Domain)

The UK variant has gained a new mutation. Notably, the additional mutation — known as E484K — is the same one found in the Brazilian and South African variants of SARS-CoV-2, but it appears to have emerged separately in the UK. 

A report published this week by Public Health England (PHE) noted the spike protein mutation E484K, found in the Brazilian and South African variants, has been detected in at least 11 UK variant sequences and that “preliminary information suggests more than one acquisition event.” In other words, a concerning mutation appears to have emerged separately on an already concerning UK variant of the virus.

If you're confused by all this talk of newly detected variants, here’s how they work. Mutations are a natural part of the virus life cycle and, over the course of the pandemic, there have been thousands of SARS-CoV-2 variants that have undergone subtle mutations, most of which are inconsequential or harmless. However, the UK variant is problematic because it features a relatively high number of mutations, including a prominent mutation — known as the N501Y mutation — on its spike protein, the part of the virus used to enter host cells and the target site of most vaccines. The Brazilian and South African variants feature this N501Y mutation along with E484K on its spike protein. Now, it looks like a small number of the UK variants in circulation have also picked up this E484K mutation. 

“The E484K mutation has now been identified in a small fraction of viruses carrying sequence differences defining the UK variant. This suggests that the UK variant is now independently acquiring the E484K change," explained Dr Jonathan Stoye, Group Leader of the Retrovirus-Host Interactions Laboratory at the Francis Crick Institute.

This is especially concerning because the E484K is thought to be the main mutation impacting vaccine efficacy. As an example, a recent trial of the Novavax COVID-19 vaccine found that it was 85.6 percent effective against the UK variant, but only around 60 percent effective against the fast-spreading South African variant.

It might sound surprising that the mutation has also emerged separately in the UK variant, but researchers say it’s not entirely unexpected.

“The acquisition may be due to recombination with one of the South African/Brazilian variant viruses that may have co-infected the same cell – as we see with different influenza viruses – but this is rarer with coronaviruses,” commented Dr Julian Tang, Honorary Associate Professor and Clinical Virologist at the University of Leicester in the UK. 

“So this may be more likely to have arisen through convergent/parallel natural selection/evolution within the human population as the virus adapts to this new host – viruses can only evolve through continuous replication.” 

“An acquisition event means that the E484K mutation has been acquired by the B.1.1.7 variant [the UK variant] during the process of virus replication and selection for virus variants that are more able to grow in the presence of an antibody response," Professor Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, added. "This is a concern. It shows that the virus is very likely to be adapting to our immune response.”

It’s too early to say how this development will affect the wider outbreak or even the UK's response to its outbreak. Nevertheless, the observation builds on the growing evidence that despite the strictest measures to delay or prevent spread, the virus is undergoing an evolution worldwide.

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