“This suggests that there is a benefit to these mutations,” says Stephen Golstein, an evolutionary virologist who studies coronaviruses at the University of Utah. “Each variant of SARS-CoV-2 ‘wants to be more transmissible’, in a sense. So the fact that so many of them land on these mutations suggests that there might be a real benefit to doing so. These different lines arrive essentially at the same solution to interact more efficiently with the human receptor, ACE2.
Like any virologist, Goldstein is reluctant to anthropomorphize his subjects. Viruses have no dreams or desires. They are smart micromachines programmed to make as many copies of themselves as possible. But one way to do this is to increase their chances of invading new hosts. SARS-CoV-2 does this by guiding the advanced protein range which coat its exterior towards a protein called ACE2 which is found outside of some human cells. The peak is encrusted with sugars that camouflage the virus from the human immune system, with the exception of the tip, known as the receptor binding domain, or RBD for short. This exposed section is the part that locks onto ACE2, changing the shape of the receptor – like a key rearranging the cups inside a lock – and allowing the virus to enter the cell and begin to replicate.
The mutations that worry scientists so much all occur in this small exposed point. And now researchers are rushing to figure out how each of them could give SARS-CoV-2 new tricks.
There is N501Y, a mutation that occurs in all three variants, which replaces the coronavirus’ 501st amino acid, asparagine, with tyrosine. Studies on cells and animal models suggest that the change allows SARS-CoV-2 to more easily cling to ACE2, which is a hypothesis as to why the variant has, at this point, been quite convincingly associated with increased transmission. The best proof for this so far came out of the UK, which performs more genomic sequencing than any other country in the world. Scientists estimate that the British variant, also known as B.1.1.7, is between 30 and 50% more infectious than other circulating strains.
In Ireland, it became the dominant version of the virus in just a matter of weeks, and it has since spread to more than 60 countries, including the United States. As of Tuesday, the United States had detected 293 cases of the British variant, according to the data from the United States Centers for Disease Control and Prevention. The agency estimates it will become dominant in the United States in March.
A Brazilian variant, also called P1, and the South African variant, sometimes called B.1.351, also have a second and third mutation in common: K417T and E484K. At the moment, scientists know more about the latter. It changes a negatively charged amino acid to a positively charged acid. In variants without this mutation, this section of RBD lies in front of a negatively charged stretch of ACE2, so they repel each other. But the E484K mutation reverses that charge, causing them to fit together tightly instead.
Minnesota reported the first case of the Brazilian variant to the United States on Monday, but so far no case of the South African variant has yet been confirmed in the United States.
Scientists at the Fred Hutchinson Cancer Research Center have found that E484K may be the most important alteration in improving the virus’s ability to evade the immune system. In laboratory experiments, they observed that antibodies in the blood of patients with Covid-19 recovered 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 fell ill in South Africa’s first wave, and they found that 90% of them had reduced immunity to the new variant containing E484K. In almost half of the samples, the new variant completely escaped pre-existing antibodies. Another study by another South African colleague, this time using a live virus, found similar results. (All are shared in pre-print– none have yet been peer reviewed, as has become common in the age of Covid.)