The CORONA VIRUS is MUTATING — does it matter ?? Dr. Tshetiz Dahal
Different SARS-CoV-2 strains haven’t yet had a major impact on the course of the pandemic, but they might in future.
When COVID-19 spread around the globe this year, i wondered how the deadly virus behind the pandemic might be changing as it passed from person to person. Compared with HIV, SARS-CoV-2 is changing much more slowly as it spreads. But one mutation was unusual . It was in the gene encoding the spike protein, which helps virus particles to penetrate cells. They saw the mutation appearing again and again in samples from people with COVID-19. At the 614th amino-acid position of the spike protein, the amino acid aspartate (D, in biochemical shorthand) was regularly being replaced by glycine (G) because of a copying fault that altered a single nucleotide in the virus’s 29,903-letter RNA code. Virologists were calling it the D614G mutation.
D614G is increasing in frequency at an alarming rate” . It had rapidly become the dominant SARS-CoV-2 lineage in Europe and had then taken hold in the United States, Canada and Australia. D614G represented a “more transmissible form of SARS-CoV-2”, the paper declared, one that had emerged as a product of natural selection.
These assertions dismayed many scientists. It wasn’t clear that the D614G viral lineage was more transmissible, or that its rise indicated anything unusual, they said. But alarm spread fast across the media. Although many news stories included researchers’ caveats, some headlines declared that the virus was mutating to become more dangerous.
The work sparked a interest in D614G. Even those who were sceptical that the mutation had changed the virus’s properties agreed that it was intriguing, because of its meteoric rise and ubiquity. For months, that lineage has been found in almost all sequenced samples of SARS-CoV-2 (see ‘Global spread’). “This variant now is the pandemic. As a result, its properties matter,” Some experiments suggest that viruses carrying the variant infect cells more easily. Other work has revealed possible good news: the variant might mean that vaccines can target SARS-CoV-2 more easily. But many scientists say there remains no solid proof that D614G has a significant effect on the spread of the virus, or that a process of natural selection explains its rise.
Soon after SARS-CoV-2 was detected in China, researchers began analysing viral samples and posting the genetic codes online. Mutations — most of them single-letter alterations between viruses from different people — allowed researchers to track the spread by linking closely related viruses, and to estimate when SARS-CoV-2 started infecting humans.
Viruses that encode their genome in RNA, such as SARS-CoV-2, HIV and influenza, tend to pick up mutations quickly as they are copied inside their hosts, because enzymes that copy RNA are prone to making errors. After the severe acute respiratory syndrome (SARS) virus began circulating in humans, for instance, it developed a kind of mutation called a deletion that might have slowed its spread.
But sequencing data suggest that coronaviruses change more slowly than most other RNA viruses, probably because of a ‘proofreading’ enzyme that corrects potentially fatal copying mistakes. A typical SARS-CoV-2 virus accumulates only two single-letter mutations per month in its genome — a rate of change about half that of influenza and one-quarter that of HIV . Despite the virus’s sluggish mutation rate, researchers have catalogued more than 12,000 mutations in SARS-CoV-2 genomes. But scientists can spot mutations faster than they can make sense of them. Many mutations will have no consequence for the virus’s ability to spread or cause disease, because they do not alter the shape of a protein, whereas those mutations that do change proteins are more likely to harm the virus than improve it (see ‘A catalogue of coronavirus mutations’). “It’s much easier to break something than it is to fix it,” says Hodcroft, who is part of Nextstrain, an effort to analyse SARS-CoV-2 genomes in real time. Many researchers suspect that if a mutation did help the virus to spread faster, it probably happened earlier, when the virus first jumped into humans or acquired the ability to move efficiently from one person to another. At a time when nearly everyone on the planet is susceptible, there is likely to be little evolutionary pressure on the virus to spread better, so even potentially beneficial mutations might not flourish. As far as the virus is concerned, every single person that it comes to is a good piece of meat .
The mutation caught eye because of its position in the spike protein, which is a major target for ‘neutralizing’ antibodies that bind to the virus and render it non-infectious. And viruses with the mutation were also rising in frequency in more than one part of the world.
D614G was first spotted in viruses collected in China and Germany in late January; most scientists suspect the mutation arose in China. It’s now almost always accompanied by three mutations in other parts of the SARS-CoV-2 genome — possible evidence that most D614G viruses share a common ancestor.
D614G’s rapid rise in Europe drew Korber’s attention. Before March — when much of the continent went into lockdown — both unmutated ‘D’ viruses and mutated ‘G’ viruses were present, with D viruses prevalent in most of the western European countries that geneticists sampled at the time. But natural selection in favour of G viruses isn’t the only, or even the most likely, explanation for this pattern. The European dominance of G variants could be simply down to chance — if, for instance, the mutation happened to be slightly more common in the viruses that arrived in Europe. A small number of individuals seem to be responsible for most of the virus’s spread, and an early, chance tilt in favour of G viruses could explain the lineage’s apparent takeover now. Such ‘founder effects’ are common in viruses, especially when they spread unchecked, as SARS-CoV-2 did in much of Europe until mid- to late March. Many scientists weren’t convinced that D614G’s rise was remarkable — or all that relevant to the pandemic. “I thought that preprint was incredibly premature,” . D614G was shaped by their work on HIV, which has found that even seemingly insignificant mutations can have a profound effect on how the immune system recognizes that virus. “We were alarmed by it, and we need to see if it’s having an effect on vaccines” .
