“This suggests that these mutations have an advantage,” says Stephen Golstein, an evolutionary virologist studying coronaviruses at the University of Utah. Every SARS-CoV-2 variant ‘wants to be more transferable’, in a sense. The fact that so many of them end up on these mutations thus suggests that it may be a real benefit to do so. These different sex lines come to essentially the same solution for how to deal more effectively with the human receptor, ACE2. ‘
Like any virologist, Goldstein hesitates to anthropomorphize his subjects. Viruses do not have dreams and desires. These are intelligent micromachines that are programmed to make as many copies of themselves as possible. But one way to do that is to increase their chances of invading new hosts. SARS-CoV-2 does this by directing the variety of peak proteins that cover the outside to a protein called ACE2 that sits on the outside of some human cells. The vein is enveloped in sugars that camouflage the virus of the human immune system, except for the tip, known as the receptor-binding domain, or RBD for short. This exposed part is the part that sounds like ACE2, changes the shape of the receptor – like a key that rearranges the tumblers inside a lock – and can cause the virus to enter the cell and start repeating.
The mutations that make scientists so worried all occur in the slightly exposed little peak. And now researchers are rushing to find out how each of them can give SARS-CoV-2 some new tricks.
There is N501Y, a mutation found in all three variants, which replaces the coronavirus’ 501st amino acid, asparagine, with tyrosine. Studies in cells and animal models suggest that the change makes it easier for SARS-CoV-2 to reach ACE2, which is one hypothesis why the variant is at this stage quite convincingly associated with increased transmission. The best proof of that so far came from the United Kingdom, which does more genomic sequencing than any other country in the world. Scientists there estimate that the British variant, alternatively known as B.1.1.7, is between 30 and 50 percent more contagious than other strains circulating.
In Ireland, it became the dominant version of the virus within a few weeks and has since spread to more than 60 countries, including the US. According to the US Centers for Disease Control and Prevention, the U.S. has detected 293 cases of the British variant as of Tuesday. The agency estimates that it will dominate in the US by March.
A Brazilian variant, also called P1, and the South African, sometimes called B.1.351, also shared a second and third mutation: K417T and E484K. Right now, scientists know more about the latter. It changes an amino acid that is negatively charged to one that is positively charged. In variants without this mutation, that portion of the RBD sits opposite a negatively charged piece of ACE2, so that they repel each other. But the E484K mutation reverses the charge, allowing it to snap tightly together.
On Monday, Minnesota reported the first case in the US on the Brazilian variant, but so far no cases of the South African variant in the US have been confirmed.
Scientists from the Fred Hutchinson Cancer Research Center have found that E484K may be the most important change in improving the virus’ ability to evade immune protection. In laboratory experiments, they observed that antibodies in the blood of recovered Covid-19 patients were 10 times less effective at neutralizing variants with the E484K mutation. In a separate study, some of De Oliveira’s colleagues tested the blood of Covid-19 patients who became ill in the first wave of South Africa, and found that 90 percent of them had a reduced immunity to the new E484K-containing variant. In almost half of the samples, the existing version completely escaped the new variant. In another study by another South African colleague, who this time used live virus, similar results were found. (All are shared as pre-prints – and have not yet been peer-reviewed, as became common in Covid’s time.)