NCURRENT SELECTION it is a powerful force. In still controversial circumstances, he took a bat coronavirus and adapted it to people. The result spread across the globe. Now, in two independent but coincident events, he has modified this virus even more, creating new variants that are replacing the original versions. It seems possible that one or the other of these new viruses will soon become a dominant form of SARS–ÇOV-two.
Their knowledge spread in mid-December. In Britain, a group of researchers called Covid-19 Genomics uK Consortium (ÇOG–youK) published the genetic sequence of the variant B.1.1.7, and NERVTAG, a group that studies emerging viral threats, informed the government that this version of the virus was 67-75% more transmissible than those already circulating in the country. Meanwhile, in South Africa, Salim Abdool Kalim, a leading epidemiologist, informed the country on all three television channels about a variant called 501.v2 that, until then, was responsible for almost 90% of new covid infections. 19 in the Western Cape province.
Britain responded on December 19, tightening restrictions already in place. South Africa’s response came on December 28, in the wake of the millionth registered case of the disease, with measures that extended the night curfew by two hours and reimposed the ban on the sale of alcohol. Other countries responded by discouraging it even more strongly than before any trip between them and Britain and South Africa. At least in the case of B.1.1.7, however, this simply closed the stable door after the horse ran away. This variant has now been detected in several countries other than Britain – and from these new locations, or from Britain, it will spread further. Isolated cases of 501.v2 outside of South Africa have also been reported in Australia, Great Britain, Japan and Switzerland.
So far, the evidence suggests that, despite their extra transmissibility, none of the new variants is more dangerous on a case-by-case basis than existing versions of the virus. In this sense, both are following 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 transmission), rather than more deadly (which reduces). And the speed with which they spread is impressive.
The first sample of B.1.1.7 was collected on September 20, south east of London. The second was found the next day in London itself. A few weeks later, in early November, B.1.1.7 was responsible for 28% of new infections in London. In the first week of December, this percentage had risen to 62%. It is probably over 90% now.
Variant 501.V2 has a similar history. It started in the Eastern Cape, the first samples dating from mid-October, and has since spread to other coastal provinces.
The rapid rise of B.1.1.7 and 501.v2 raises several questions. One is why these specific variants have been so successful. The second is in what circumstances they arose. The third is whether they will resist any of the new vaccines in which this stock is being placed.
The answers to the first of these questions are in the genomes of the variants. ÇOG–youKinvestigation of B.1.1.7 shows that it differs significantly from the original version of SARS–COV-2 out of 17 places. This is too much. In addition, several of these differences are in the gene for spike, the protein by which coronaviruses bind to their cell prey. Three of the peak mutations caught the researchers’ attention.
1, N501Y, affects the 501st link in the peak 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 main points of contact that help fix the peak on its target, a protein called AT2 that occurs in the superficial 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 (“N”, In biological abbreviation) by a so-called tyrosine (“Y”). This is important because previous laboratory work has shown that the change in chemical properties that this substitution causes binds the two proteins more tightly than normal. Perhaps tellingly, this particular mutation (though none other) is shared with 501.Vtwo
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B.The other two intriguing peak mutations of 1.1.7 are 69-70del, which eliminates two amino acids from the chain completely, and P681H, which replaces yet another amino acid, histidine, with a so-called proline at the 681 chain link. The double deletion attracted the attention of researchers for several reasons, including the fact that it was also found in a viral variant that afflicted some mink producers. in Denmark in November, raising concerns about the development of an animal reservoir for the disease. The substitution is considered significant because it is at one end of a part of the protein called a s1 /s2 furin cleavage site (links 681-688), which helps activate the peak in preparation for its encounter with the target cell. This site is absent from related peak coronavirus proteins, like the original SARS, and it may be a reason why SARS–ÇOV-2 is so infectious.
The South African variant, 501.v2, has only three significant mutations, all of which are in the spike receptor binding domain. Besides N501Y, they are K417N and AND484K (K and AND are amino acids called lysine and glutamic acid). These two other links are now subject to intense scrutiny.
Even three significant mutations are enough for one variant to have. Only one would be more common. The 17 found in B.1.1.7, therefore, constitute a major anomaly. How this infinity of changes came together in a single virus is therefore the second question that needs an answer.
The authors of ÇOG–UK paper has a suggestion. This is that, instead of being a casual accumulation of changes, B.1.1.7 may be the result of an evolutionary process – but it happened in a single human being, and not in a population. They note that some people develop chronic covid-19 infections because their immune systems are not functioning properly and therefore cannot eliminate the infection. These unfortunates, they suppose, can act as incubators for new viral variants.
The theory is like that. At first, this patient’s lack of natural immunity relaxes the pressure on the virus, allowing for the multiplication of mutations that would otherwise be eliminated by the immune system. However, treatment for chronic covid-19 often involves what is known as convalescent plasma. This is the serum collected from recovered infected patients, which is therefore rich in antibodies against SARS–ÇOV-two. As a therapy, this approach often works. But administering such a cocktail of antibodies applies strong selection pressure to what is now a diverse viral population in the patient’s body. This the ÇOG–UK the researchers estimate, may result in the success of mutational combinations that would not otherwise have seen the light of day. It is possible that B.1.1.7 is one of them.
The answer to the third question – whether any of the new variants will resist the vaccines being launched – is “probably not”. It would be a long-standing coincidence if mutations that spread in the absence of a vaccine protect the virus that carries them from the immune response generated by that 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 induced by a vaccine, then there is a good chance that nature will find it.■
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This article appeared in the Science and Technology section of the print edition under the title “Variations on a theme”