Should we fear an endless epidemic as new variants of SARS-CoV-2 emerge daily around the world? Not necessarily, because these new variants actually share many mutations, indicating that the virus has a relatively limited number of ways to recombine its genome without damaging its fundamental structure.
English, South African, Brazilian, California, Moroccan, Filipino, Egyptian and Tunisian variants: The SARS-CoV-2 coronavirus is constantly mutating. With each replication, a few letters of the genetic code are probably changed. The more the virus spreads, the more often it replicates and the more likely it is to mutate. This already raises fears of a never-ending epidemic, in which new variants would constantly emerge, escaping antibodies and vaccines. However, when the different variants are examined in detail, most of them show the same mutations, suggesting that the virus’s ability to transform is in fact quite limited.
First, most mutations affect non-coding parts of the virus. Second, many mutations go undetected, either because they have no effect on the activity of the virus or because they provide no competitive advantage and therefore disappear quickly. Moreover, too many mutations would destroy the viral machinery and make it non-viable or inefficient. So the spike protein must maintain a certain shape to stick effectively to the cell, says Shane Crotty of the Immunology Institute in La Jolla, California. “It’s like putting your foot in a shoe: The shoe has to be the right shape and size, and it has to be recognized as a shoe.”
The convergent evolution hypothesis
In his laboratory at the Pittsburgh Center for Evolutionary Biology and Medicine, microbiologist Vaughn Cooper has studied the genomes of thousands of strains of SARS-CoV-2 and observed “convergent evolution,” in which amino acid substitutions always occur in the same place. “Our laboratory has found at least seven genetically independent lines that have acquired a mutation at a specific site in the spike protein,” notes the researcher. In six of the seven lines, the amino acid glutamine (denoted by Q) is converted to histidine (H) at position 677 (the mutation is therefore called 677H). This particular mutation is found in many independent lines, in Egypt, Denmark, India, and Macedonia. “The seven lines we studied also have a mutation called S:614G, which was identified a few months ago as the first significant change in the virus and has become so widespread that it is now found in 90 percent of all infections,” Cooper says.
And these are by no means the only examples of convergent evolution, the researcher points out: “Many variants such as B.1.351 [South African], B.1.1.7 [English variant], P.1 [Brazilian] and P.3 [Filipino] share combinations of mutations at positions 18, 69, 70, 417, 452, 501, 681, as well as the E484K mutation, which allows the virus to partially evade neutralizing antibodies.
‘You can think of convergent evolution as a game of Tetris, where a limited number of building blocks can be assembled in different ways to achieve the same winning structures,’ says Vaughn Cooper. ‘For example, we know that the combination of mutations in B.1.1.7 makes it particularly infectious and that the B.1.351 line can escape antibodies through E484K.
Less than 1% of the mutations are truly dangerous
These mutations that give the virus a competitive advantage are actually limited. “The new variants are really just a repeat of mutations found in other established strains. So we can expect the virus to gradually run out of new opportunities for major adaptations,” says Vaughn Cooper. According to Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Center in Seattle, less than 1% of the mutations would actually make the virus resistant to antibodies.
Unfortunately, in addition to mutations, the virus can also recombine when two different strains occur simultaneously in an organism. Furthermore, these recombinations are more dangerous because they involve changes in large parts of the genome. Even assuming that the coronavirus remains stable, it will still be necessary to vaccinate every year people who have not been vaccinated yet or those whose antibody levels have become too low.