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Worrisome new coronavirus strains are emerging. Why now?

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https://www.wired.com/story/worrisome-ne...g-why-now/

EXCERPTS: All viruses mutate. They are, after all, just autonomous bits of protein-encased, self-replicating strings of code equipped with imperfect internal spell-checkers. Make enough copies and there are bound to be mistakes. Coronaviruses actually make fewer mistakes than most. This one, SARS-CoV-2, evolves at a rate of about 1,100 changes per location in the genome annually—or about one substitution every 11 days.

The predictable pace at which the coronavirus’s genetic building blocks shift around can be detected by genomic sequencing, which allows scientists to identify new strains and follow them as they spread through a population or fade away. For most of 2020, those random changes didn’t have much of an effect on the way the virus behaves. But recently, three notable mutations have begun to show up alone or in combination with each other. And everywhere they do, these versions of the virus tend to quickly outcompete other circulating strains.
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“That suggests there’s an advantage to these mutations,” says Stephen Golstein, an evolutionary virologist who studies coronaviruses at the University of Utah. “Every SARS-CoV-2 variant ‘wants to be more transmissible,’ in a sense. So the fact that so many of them are landing on these mutations suggest there could be a real benefit for doing so. These different lineages are essentially arriving at the same solution for how to interact more efficiently with the human receptor, ACE2.”

[...] Before SARS-CoV-2 crossed into humans, it had been circulating inside bats for millions of years. And when scientists began taking a closer look at the bat version of ACE2, they found a staggering diversity of the gene that codes for that protein. What they were seeing were the genetic scars of an evolutionary arms race. Bat populations had lived with SARS-CoV-2 for long enough that their ACE2 receptors had started changing—morphing in shape so that they became harder for the virus to grab onto. And in turn, SARS-CoV-2 had evolved to try to fit into those new shapes. Eventually, one of those descendants looked enough like the human ACE2 receptor that it could make the cross-species leap (with perhaps an intermediary host in there somewhere).

There are two major evolutionary forces driving diversification of the spike protein: interacting with ACE2, and getting clobbered by neutralizing antibodies. In the human population, a year isn’t long enough for new versions of ACE2 to crop up and be passed on to a new generation of people. And ACE2 plays a key role in regulating blood pressure, wound healing, and other essential functions, so any genetic changes that impair its ability to do those things would likely not get very far, even if they made it more difficult for the coronavirus to start an infection.

So if the evolution of the ACE2 receptor can’t rescue us in the short term, that leaves the body’s immune system, and the armies of cells that orchestrate ejecting any unwanted visitors from it. Many pathogens mutate their proteins toward new shapes to avoid being recognized by the antibodies that would normally adhere to them, blocking their entry into cells. That’s called antigenic drift. And that’s what some scientists think drove the emergence of the Brazil and South African variants.

[...] Goldstein has a simpler explanation, one that’s beginning to get more traction in the scientific community. The convergent evolution of wilier versions of the virus might just be a consequence of so many poorly managed government pandemic responses, which didn’t marshal sufficient resources or inspire the kind of collective action required to not just crush the initial curve, but keep it crushed. “The fact that we lost control in so many places in the fall allowed for the ballooning of this incredibly huge viral population size,” says Goldstein. That created the opportunity for that many more mutations to happen, and in some places, the right circumstances for some particularly insidious ones to get selected.

[...] Scientists may never get a clear answer to exactly where and under what conditions these new variants emerged. But de Oliveira isn’t so sure it matters. “The one thing we know for sure is that if you keep the virus circulating long enough, it will develop escape mutations,” he says.

The much more pressing question, then, is to what degree will such mutations affect efforts to vaccinate our way out of the pandemic? [...] Moderna scientists and their partners at the National Institutes of Health released the not-yet-peer-reviewed results of their own lab experiments using blood from people who had received the company’s vaccine. Although antibodies from immunized people fended off the UK variant just fine, they found, the South African variant caused some issues. Against that strain, the neutralizing power of the antibodies induced by Moderna’s vaccine was reduced six-fold, though they still functioned at levels believed to be effective.

In a statement, Moderna CEO Stéphane Bancel said that he is confident the company’s vaccine should still be protective against the newly detected variants, but that “it is imperative to be proactive as the virus evolves.” To that end, Moderna’s scientists are retooling the company’s mRNA sequence to more closely mimic the most significant mutations and plan to test it as an additional booster shot in clinical studies later this year.

“We shouldn’t panic yet, but we should be careful. This is a warning,” says Hatziioannou. “If the virus continues to accumulate mutations in its spike protein, we run the risk of the efficacy of vaccines diminishing further.” (MORE - details)
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