“This suggests that there is an advantage to these mutations,” says Stephen Golstein, an evolutionary virologist who studies coronavirus at the University of Utah. “Each variant of SARS-CoV-2 ‘wants to be more transmissible’, in a sense. Therefore, the fact that so many of them are landing on these mutations suggests that there may be a real benefit in doing so. These different strains are essentially coming up with the same solution on how to interact more efficiently with the human receptor, ACE2. “
Like any virologist, Goldstein hesitates to anthropomorphize his subjects. Viruses have no dreams and desires. They are intelligent micromachines programmed to make as many copies of themselves as possible. But one way to do this is to increase your chances of breaking into new hosts. SARS-CoV-2 does this by guiding the set of peak proteins that line its exterior towards a protein called ACE2 that sits outside some human cells. The peak is embedded in sugars that camouflage the human immune system virus, except for the tip, known as the receptor-binding domain, or RBD. This exposed section is the part that clings to ACE2, changing the shape of the receptor – like a key rearranging the hooks inside a lock – and allowing the virus to enter the cell and start to replicate.
All the mutations that concern scientists occur at that small exposed peak. And now researchers are racing to find out how each of them may be giving SARS-CoV-2 some new tricks.
There is N501Y, a mutation that occurs in all three variants, which replaces the 501st amino acid in the coronavirus, asparagine, with tyrosine. Studies in cells and animal models suggest that the change makes it easier for SARS-CoV-2 to cling to ACE2, which is a hypothesis as to why the variant was, in this point, quite convincingly associated with increased transmission. The best evidence of this so far left the UK, which is doing more genomic sequencing than any other country in the world. Scientists estimate that the UK variant, alternatively known as B.1.1.7, is between 30 and 50 percent more infectious than other circulating strains.
In Ireland, it became the dominant version of the virus in just a few weeks and has since spread to more than 60 countries, including the United States. As of Tuesday, the United States had detected 293 cases of the United Kingdom variant, according to 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 mutations in common: K417T and E484K. At this point, scientists know more about the latter. It changes a negatively charged amino acid to a positively charged one. In variants without this mutation, this section of the RBD faces a negatively charged stretch of ACE2, so they repel each other. But the E484K mutation reverses that charge, making them fit well together.
On Monday, Minnesota reported the first American case of the Brazilian variant, but so far no case of the South African variant has been confirmed in the United States.
Scientists at Fred Hutchinson Cancer Research Center have found that E484K may be the most important change when it comes to increasing the virus’s ability to escape immune defenses. In laboratory experiments, they found that antibodies in the blood of patients recovered from Covid-19 were 10 times less effective in neutralizing variants with the E484K mutation. In a separate study, some of Oliveira’s colleagues tested the blood of Covid-19 patients who fell ill in South Africa’s first wave and found that 90% of them had some reduced immunity to the new variant containing E484K. In almost half of the samples, the new variant completely escaped the pre-existing antibodies. Another study by another South African colleague, this time using live viruses, found similar results. (All are being shared as pre-impressions – neither has yet been peer-reviewed, as has become common in the Covid era.)