“That suggests that these mutations have an advantage,” said Stephen Golstein, an evolutionary virologist who studies coronaviruses at the University of Utah. “In a sense, each SARS-CoV-2 variant ‘wants to be’ more transferable ‘. So the fact that so many of them land on these mutations suggests this could have a real benefit. These different sexes essentially come to the same solution for a more efficient interaction with the human receptor, ACE2. “
Like any virologist, Goldstein is hesitant to anthropomorphize his subjects. Viruses have no dreams and desires. They are intelligent micro-machines 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 series of spike proteins that coat its outside to a protein called ACE2 that resides on the outside of some human cells. The peak is covered in sugars that camouflage the virus from the human immune system, except for the very tip, known as the receptor binding domain, or RBD for short. This exposed part is the part that locks onto ACE2, changing the shape of the receptor – like a key rearranging the cups in a lock – and allowing the virus to enter the cell and start multiplying.
The mutations that worry scientists so much are all in that little exposed patch of peak. And now researchers are racing to find out how each of them could give SARS-CoV-2 a few new tricks.
There is N501Y, a mutation that occurs in all three variants, which replaces the 501st amino acid of the coronavirus, asparagine, with tyrosine. Studies in cells and animal models suggest that the change makes it easier for SARS-CoV-2 to grasp ACE2, which is one hypothesis as to why the variant is quite convincingly associated with increased transmission at this point. The best proof of that so far came from the UK, which does more genomic sequencing than any other country in the world. Scientists there estimate that the British variety, also known as B.1.1.7, is between 30 and 50 percent more contagious than other circulating strains.
In Ireland, it became the dominant version of the virus in just weeks, and it has since spread to more than 60 countries, including the US. According to data from the U.S. Centers for Disease Control and Prevention, the U.S. had detected 293 cases of the British variant as of Tuesday. The agency estimates it will become dominant in the US in March.
A Brazilian variant, also called P1, and the South African variant, also called B.1.351, also share a second and third mutation: K417T and E484K. Scientists currently know more about the latter. It turns an amino acid that was negatively charged into a positively charged amino acid. In variants without this mutation, that part of the RBD sits opposite a negatively charged piece of ACE2, so they repel each other. But the E484K mutation reverses that charge, causing them to click tightly together instead.
On Monday, Minnesota reported the first case of the US variant of the Brazilian variant, but no cases of the South African variant have been confirmed in the US so far.
Scientists at the Fred Hutchinson Cancer Research Center found that E484K is perhaps the most important change when it comes to improving the virus’s ability to evade immune defenses. In laboratory experiments they saw that antibodies in the blood of recovered Covid-19 patients were 10 times less effective in 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 during the first wave of South Africa, and found that 90 percent of them had decreased immunity to the new E484K-containing variant. In almost half of the samples, the new variant completely escaped the pre-existing antibodies. Another study by another South African colleague, this time with live virus, yielded similar results. (All are shared as preprints – neither of which has yet been peer-reviewed, as has become common in the Covid era.)