Natural selection is a powerful force. In circumstances that are still disputed, it took a bat coronavirus and adapted it to people instead. The result has spread around the globe. Now, in two independent but coincidental events, it has modified that virus still further, creating new variants which are displacing the original versions. It looks possible that one or other of these novel viruses will itself soon become a dominant form of sars–cov-2.
Source: The Economist
Reprinted for educational purposes and social benefit, not for profit.
Knowledge of both became widespread in mid-December. In Britain, a set of researchers called the Covid-19 Genomics uk Consortium (cog–uk) published the genetic sequence of variant b.1.1.7, and nervtag, a group that studies emerging viral threats, advised the government that this version of the virus was 67-75% more transmissible than those already circulating in the country. In South Africa, meanwhile, Salim Abdool Kalim, a leading epidemiologist, briefed the country on all three television channels about a variant called 501.v2 which, by then, was accounting for almost 90% of new covid-19 infections in the province of Western Cape.
Britain responded on December 19th, by tightening restrictions already in place. South Africa’s response came on December 28th, in the wake of its millionth recorded case of the illness, with measures that extended a night-time curfew by two hours and reimposed a ban on the sale of alcohol. Other countries have reacted by discouraging even more forcefully than before any travel between themselves and Britain and South Africa. At least in the case of b.1.1.7, though, this has merely shut the stable door after the horse has bolted. That variant has now been detected in a score of countries besides Britain—and from these new sites, or from Britain, it will spread still further. Isolated cases of 501.v2 outside South Africa have been reported, too, from Australia, Britain, Japan and Switzerland. So far, the evidence suggests that despite their extra transmissibility, neither new variant is more dangerous on a case-by-case basis than existing versions of the virus. In this, both are travelling the path predicted by evolutionary biologists to lead to long-term success for a new pathogen—which is to become more contagious (which increases the chance of onward transmission) rather than more deadly (which reduces it). And the speed with which they have spread is impressive.
The first sample of b.1.1.7 was collected on September 20th, to the south-east of London. The second was found the following day in London itself. A few weeks later, at the beginning of November, b.1.1.7 accounted for 28% of new infections in London. By the first week of December that had risen to 62%. It is probably now above 90%. Variant 501.v2 has a similar history. It began 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 particular variants have been so successful. A second is what circumstances they arose in. A third is whether they will resist any of the new vaccines in which such store is now being placed. The answers to the first of these questions lie in the variants’ genomes. cog-uk’s investigation of b.1.1.7 shows that it differs meaningfully from the original version of sars-cov-2 in 17 places. That is a lot. Moreover, several of these differences are in the gene for spike, the protein by which coronaviruses attach themselves to their cellular prey. Three of the spike mutations particularly caught the researchers’ eyes. One, n501y, affects the 501st link in spike’s amino-acid chain. This link is part of a structure called the receptor-binding domain, which stretches from links 319 to 541. It is one of six key contact points that 541. It is one of six key contact points that help lock spike onto its target, a protein called ace2 which occurs on the surface membranes of certain cells lining the airways of the lungs. The letters in the mutation’s name refer to the replacement of an amino acid called asparagine (“n”, in biological shorthand) by one called tyrosine (“y”). That matters because previous laboratory work has shown that the change in chemical properties which this substitution causes binds the two proteins together more tightly than normal. Perhaps tellingly, this particular mutation (though no other) is shared with 501.v2. Golden spike b.1.1.7’s other two intriguing spike mutations are 69-70del, which knocks two amino acids out of the chain altogether, and p681h, which substitutes yet another amino acid, histidine, for one called proline at chain-link 681. The double-deletion attracted the researchers’ attention for several reasons, not the least being that it was also found in a viral variant which a#icted some farmed mink in Denmark in November, causing worries about an animal reservoir of the disease developing. The substitution is reckoned signi!cant because it is at one end of a part of the protein called the s1/s2 furin-cleavage site (links 681-688), which helps activate spike in preparation for its encounter with the target cell. This site is absent from the spike proteins of related coronaviruses, such as the original sars, and may be one reason why sars-cov-2 is so infective.
The South African variant, 501.v2, has only three meaningful mutations, and all are in spike’s receptor-binding domain. Besides n501y, they are k417n and e484k (k and e are amino acids called lysine and glutamic acid). These two other links are now the subject of intense scrutiny. Even three meaningful mutations is quite a lot for a variant to have. Just one would be more usual. The 17 found in b.1.1.7 therefore constitute a huge anomaly. How this plethora of changes came together in a single virus is thus the second question which needs an answer. The authors of the cog-uk paper have a suggestion. This is that, rather than being a chance accumulation of changes, b.1.1.7 might itself be the consequence of an evolutionary process—but one that happened in a single human being rather than a population. They observe that some people develop chronic covid-19 infections because their immune systems do not work properly and so cannot clear the infection. These unfortunates, they hypothesise, may act as incubators for novel viral variants. The theory goes like this. At first, such a patient’s lack of natural immunity relaxes pressure on the virus, permitting the multiplication of mutations which would otherwise be culled by the immune system. However, treatment for chronic covid-19 often involves what is known as convalescent plasma. This is serum gathered from recovered covid patients, which is therefore rich in antibodies against sars-cov-2. As a therapy, that approach frequently works. But administering such a cocktail of antibodies applies a strong selection pressure to what is now a diverse viral population in the patient’s body. This, the cog-uk researchers reckon, may result in the success of mutational combinations which would not otherwise have seen the light of day. It is possible that b.1.1.7 is one of these.