AATURAL SELECTION is a powerful force. In circumstances that are still disputed, it took a bat coronavirus and rather adapted it in humans. The result spread all over the world. Now, in two independent but coincidental events, it has changed the virus even further and created new variants that supplant the original versions. It seems possible that some of these new viruses will soon become a dominant form of SARS–CoV-2.
Knowledge of both became widespread in mid-December. In Britain, a set of researchers called the Covid-19 Genomics uK Consortium (COG–YOUK) published the genetic sequence of variant B.1.1.7, and AERVTAG, a group looking for viral threats, advised the government that this version of the virus is 67-75% more transmissible than those already spreading in the country. In South Africa, Salim Abdool Kalim, a leading epidemiologist, informed the country on all three television channels about a variant called 501.v2, which was then responsible for almost 90% of the new covid-19 infections in the province. Western Cape.
Britain responded to this on 19 December by tightening the restrictions that already apply. South Africa’s response comes on 28 December, following its millionth case of illness, with measures extending the night clock by two hours and reintroducing a ban on the sale of alcohol. Other countries responded by discouraging any travel between Britain and South Africa even more vigorously than before. At least in the case of B.1.1.7, but it only locked the stable door after the horse bolted. This variant has now been detected in a number of countries besides Britain – and from these new sites, or from Britain, it will spread even further. Isolated cases of 501.v2 outside South Africa from Australia, Britain, Japan and Switzerland have also been reported.
So far, the evidence suggests that no new variant, despite its extra transmissibility, is more dangerous per case than existing versions of the virus. In this, both travel the path predicted by evolutionary biologists to lead to long-term success for a new pathogen – which will become more contagious (which increases the chance of continuous transmission) rather than lethal (which reduces it). And the speed with which they spread out is impressive.
The first example of B.1.1.7 was collected on 20 September in south-east London. The second was found the following day in London itself. A few weeks later, in early November, B.1.1.7 was responsible for 28% of new infections in London. By the first week of December, it had risen to 62%. It is probably now above 90%.
Variant 501.V2 has a similar history. It started in the Eastern Cape, the first specimens dating from mid-October, and has since spread to other coastal provinces.
The rapid rise of B.1.1.7 and 501.v2 raise several questions. The one is why these particular variants were so successful. “A second is in what circumstances they originated.” A third is whether they will resist any of the new vaccines in which the store is now being placed.
The answers to the first of these questions lie in the variants of the variants. COG–YOUK‘s investigation of B.1.1.7 shows that it differs significantly from the original version of SARS–COV-2 in 17 places. It is very. In addition, several of these differences are in the gene for vein, the protein with which coronaviruses attach themselves to their cellular prey. Three of the peak mutations attracted the attention of researchers in particular.
One, A501Y, affects the 501st link in the peak’s amino acid chain. This link is part of a structure called the receptor-binding domain, which extends from links 319 to 541. It is one of the six most important contact points that help bind the target, a protein called ACE2 which occurs on the surface membranes of certain cells that line the airways of the lungs. The letters in the name of the mutation refer to the replacement of an amino acid called asparagine (‘A“, In biological shorthand) by one called tyrosine (“Y”). This is important because previous laboratory work has shown that the change in chemical properties that cause this substitution binds the two proteins more tightly than normal. It is perhaps telling that this particular mutation (though no other) is shared with 501.V2.
B.1.1.7’s other two intriguing peak mutations are 69-70del, knocking two amino acids completely out of the chain, and P681H, which replaces yet another amino acid, histidine, with one called proline at chain link 681. The double scraping attracted the attention of researchers for several reasons, not least that it was also found in a viral variant that some cultivated mink in Denmark in November, raising concerns about the development of an animal reservoir of the disease. The substitution is considered important because it is on one side of a part of the protein, called S1 /S2 furin-splitting site (links 681-688), which helps to activate spike in preparation for the encounter with the target cell. This site is absent from the peak proteins of related coronaviruses, such as the original SARS, and may be one reason why SARS–CoV-2 is so infected.
The South African variant, 501.v2, has only three significant mutations, and all are in the spike’s receptor binding domain. Besides A501Y, they are K417A and E484K (K and E are amino acids called lysine and glutamic acid). These two other links are now being intensively investigated.
Even three significant mutations are many for a variant to have. Only one would be more frequent. The 17 found in B.1.1.7 therefore forms a large deviation. How this abundance of changes came together in a single virus is therefore the second question that needs an answer.
The authors of the COG–United Kingdom paper has a suggestion. It is that, rather than being a random accumulation of change, B.1.1.7 may itself be the result of an evolutionary process – but one that took place in a single human being rather than in a population. They note that some people develop chronic infections with covid-19 because their immune system does not work well and therefore cannot clear up the infection. They suspect that these unfortunates could serve as incubators for new viral variants.
The theory goes like this. Initially, the lack of natural immunity of such a patient eases the pressure on the virus, allowing the proliferation of mutations, which can otherwise be eliminated by the immune system. However, treatment for chronic covid-19 often involves the so-called recovery plasma. It is serum collected from recovered covid patients, which is therefore rich in antibodies SARS–CoV-2. As a therapy, the approach works regularly. However, the administration of such cocktail antibodies exerts a strong selection pressure on a varied viral population in the patient’s body. This, the CoG–United Kingdom researchers reckon, could result in the success of mutation combinations, which otherwise would not see the light of day. It is possible that B.1.1.7 is one of these.
The answer to the third question – whether the new variant will not be able to resist the vaccines – is probably not. It would be a long coincidence if mutations spread in the absence of a vaccine protect the virus they carry against the immune response caused by the vaccine.
However, this is no guarantee for the future. The rapid emergence of these two variants shows the power of evolution. If there is a combination of mutations that can circumvent the immune response that a vaccine causes, chances are nature will find it.■
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This article appears in the Science & Technology section of the print edition under the heading “Variations on a theme”