“This suggests that there is an advantage to these mutations,” says Stephen Golstein, an evolutionary virologist who studies coronaviruses at the University of Utah. Each SARS-CoV-2 variant “wants to be more transmissible” in a sense. So the fact that so many of them land on these mutations suggests that there could be a real benefit in this regard. These different lines come to essentially the same solution for how to interact more effectively with the human receptor, ACE2. ”
Like any virologist, Goldstein is reluctant to anthropomorphize his subjects. Viruses do not have dreams and desires. They are intelligent micro-machines programmed to make as many copies of them 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 range of spike proteins that cover its outside to a protein called ACE2 that is on the outside of human cells. The peak is encrusted in sugars that camouflage the virus from the human immune system, except for the tip, known as the receptor binding domain, or RBD for short. This exposed section is the part that locks on ACE2, changing the shape of the receptor – like a key that rearranges the glasses inside a lock – and allows the virus to enter the cell and begin to replicate.
The mutations that scientists are so worried about appear in that little exposed peak. And now researchers are struggling to find out how each of them could offer 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 cells and animal models suggest that the change makes it easier for SARS-CoV-2 to pick up ACE2, which is a hypothesis as to why the variant was, at this time, quite convincingly associated with increased transmission. The best proof of that so far came out of Britain, which does more genomic sequencing than any other country in the world. Scientists estimate that the British version, known as B.1.1.7, is 30-50% 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 US had detected 293 cases of the British variant, according to data from the US Centers for Disease Control and Prevention. The agency estimates that it will become dominant in the US by March.
A Brazilian variant, also called P1, and the South African variant, sometimes called B.1.351, have a second and third mutation in common: K417T and E484K. At this point, scientists know more about the latter. Replace an amino acid that has been negatively charged with a positively charged one. In variants without this mutation, that section of the RBD is opposite a negatively charged stretch of ACE2, so they repel each other. But the E484K mutation reverses that load, causing it to cling tightly.
On Monday, Minnesota reported the first US case of the Brazil variant, but so far no cases of the South African variant in the USA have been confirmed.
Scientists at the Fred Hutchinson Cancer Research Center have found that E484K may be the most important change when it comes to improving the virus’s ability to evade immune defense. In laboratory experiments, they observed that the antibodies in the blood of patients with recovered 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 patients with Covid-19 who became ill in the first wave in South Africa and found that 90% of them had reduced immunity to the new variant. containing E484K. In almost half of the samples, the new variant completely got rid of the pre-existing antibodies. Another study by another colleague in South Africa, this time using the live virus, found similar results. (All are shared as prepresses – none of which have yet been evaluated by colleagues, as was commonplace in Covid’s time.)