“This suggests that there is an advantage in these mutations,” says Stephen Golstein, an evolutionary virologist who studies coronaviruses at the University of Utah. “All variants of SARS-CoV-2” want to be more transmissible “in a sense. Therefore, the fact that so many of them land on these mutations suggests that there could be a real benefit. These different lineages come essentially to the same solution to interact more efficiently with the human receptor, ACE2 “.
Like any virologist, Goldstein hesitates to anthropomorphize his subjects. Viruses have no dreams or desires. They are smart micromachines programmed to make the maximum number of copies of themselves. But one way to do that is to increase the chances of invading new hosts. SARS-CoV-2 does this by guiding the range of cutting-edge proteins that line its exterior to a protein called ACE2 that is found on the outside of some human cells. The ear is embedded in sugars that camouflage the virus from the human immune system, except for the tip, known as the receptor-binding domain, or RBD in short. This exposed section is the part that sticks to ACE2, changing the shape of the receptor — like a key that rearranges the vessels inside a lock — and allows the virus to enter the cell and begin to reproduce.
All the mutations that concern scientists occur in this little exposed spike. And now researchers are rushing to find out how each of them could give SARS-CoV-2 some 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 animal cells and 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 has been so convincingly associated with an increase in transmission. The best proof of this so far has left the UK, which is doing more genomic sequencing than any other country in the world. Scientists estimate that the UK variant, also known as B.1.1.7, is 30 to 50 percent more infectious than other circulating strains.
In Ireland, it became the dominant version of the virus in 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 British variant, according to data from the U.S. 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. Right now, scientists know more about the latter. Change a negatively charged amino acid for a positively charged one. In variants without this mutation, this section of the RBD is faced with a negatively charged stretch of ACE2, so that they repel each other. But the E484K mutation reverses that load, making them come together perfectly.
On Monday, Minnesota reported the first U.S. case of the Brazil variant, but so far no case of the South African variant in the United States has been confirmed.
Scientists at the Fred Hutchinson Cancer Research Center found that E484K could be the most important alteration in improving the virus’ ability to bypass immune defenses. In laboratory experiments, they observed that antibodies in the blood of patients recovered from Covid-19 were 10 times less effective in neutralizing variants possessing the E484K mutation. In a separate study, some of De Oliveira’s colleagues tested the blood of Covid-19 patients who fell ill in the first wave of South Africa and found that 90% of them had reduced immunity to the new variant that contained E484K. In almost half of the samples, the new variant completely escaped the pre-existing antibodies. Another study by another South African colleague, who this time used live virus, found similar results. (All are shared as prepresses, neither has yet been revised in pairs, as was customary in Covid’s time).