Small mutations with big consequences
According to the World Health Organization (WHO), variant viruses are classified as either variants of concern or variants of interest, and as of May 31, 2021, assigned labels based on the Greek alphabet (See update).
For variants of concern like B.1.1.7, B.1.351 and P.1, there is concrete evidence available that its mutations increase the virus’ transmissibility and disease severity. In contrast, for variants of interest like B.1.427, B.1.429, B.1.617 and B.1.617.2, the evidence is more preliminary—requiring further monitoring and follow-up studies.
Among the variants in the figure below, B.1.1.7—which emerged in the United Kingdom (UK)—is perhaps the most widespread, having been found in over 110 countries. Believed to be up to 50 percent more infectious than the wildtype SARS-CoV-2 virus, B.1.1.7 features several mutations that may help it better infect human cells.
For instance, replacing the amino acid asparagine (N) in the spike protein’s 501st position with tyrosine (Y), as in the mutation N501Y, may alter the spike protein’s shape for a tighter fit with human cells. Accordingly, N501Y has also independently surfaced in other variants of concerns such as B.1.351, first detected in South Africa, and P.1, first detected in Brazil. Meanwhile, D614G—an early mutation now found in all variants of concern—stabilizes the spike protein, while P681H may facilitate viral binding to the human cell.
Compared to B.1.1.7, the two other variants of concern are more closely related, sharing two other notable mutations. Though the scientific jury is still out, the K417N or K417T mutation respectively found in B.1.351 and P.1 may also help the spike protein latch tightly onto human cells. But it’s their E484K mutation—also known as Eek—that’s received more attention.
As it occurs near the top of SARS-CoV-2’s spike protein, scientists theorize that Eek may alter the protein’s shape to help it avoid antibodies. Indeed, Johnson & Johnson’s (J&J) vaccine was 72 percent effective against moderate to severe COVID-19 in the US, but only 57 percent effective in South Africa—indicating B.1.351’s enhanced ability to evade the immune system. A similar mutation, E484Q, is also found in B.1.617 and B.1.617.2 variants of interest first detected in India.
“We’ve seen Eek emerge independently in different parts of the world. It is possible that this mutation could have emerged from an immunocompromised COVID-19 patient or from the continuous transmission of the virus in the local population,” said Saloma.
Other variants of interest to emerge in recent months are B.1.427 and B.1.429 which were first found in California, USA. While these variants lack Eek, they do share the L452R mutation with the lineages detected in India. As B.1.427 and B.1.429 are both around 20 percent more transmissible compared to the wildtype virus, scientists believe that L452R may stabilize the spike protein for better binding to human cells, much like D614G.
