Saturday, February 27

COVID-19 is mutating. What that means, is anyones guess | INFORUM – INFORUM

It has mutated.

Though a random event, a variant is now born. It happens constantly. Fortunately, most of these accidents have no effect on infection, spread, or illness severity and soon disappear. The useful ones, however, the ones that help the virus replicate faster, create champions that can replace previous variants. These are called a strain.

Some virologists believe SARS-CoV-2 emerged through the meeting of a horseshoe bat and a so-called “reservoir” host (like a pangolin) over one year ago. Others believe the virus had already circulated quietly in animals and humans long before mutating into the form that took flight in late 2019. Either way, the virus that causes COVID-19 has been mutating for a year now.

A new paper from a team of doctoral students in the School of Information Sciences at the University of Illinois has charted the rate of mutation in the 29 proteins that make up SARS-CoV-2. These details matter because if a protein is mutating a lot — experiencing high levels of entropy — it is effectively a moving target, and that’s bad for vaccines.

The good news, the authors report, is that a portion of their findings offer hope for the vaccines now headed to market — at least at the outset. The bad news, they add, is that there are multiple “regions of intrinsic disorder” on the protein structure of the virus, that could mean trouble for those vaccines over time.

But at least the makers of future vaccines will know to target those regions next.

“The spike protein story is a good result,” says lead author Gustavo Caetano-Anolles. He speaks here of the paper’s finding that the mutations to the SARS-CoV-2 spike protein have slowed over the course of the past year, the spike that protrudes from all coronaviruses having by now become a familiar presence in our lives.

As the landing gear needed to latch SARS-CoV-2 onto ACE2 receptors in the lungs, the COVID-19 spikes will soon become the targets of two COVID-19 vaccines expected to receive approval first. The Pfizer and Moderna products use mRNA — a synthesized set of genetic instructions that direct the body to produce a surplus of free-floating spikes, readying the immune system to go after them when they eventually arrive attached to SARS-CoV-2.

LIke others before them, Caetano-Anolles’ team has learned that the protein controlling the spike (it is called G614D) has become less mutable over the course of this past year. That means the vaccines soon to be shipped were built to take on something that will not change very much. “It tells you the spike mutation is becoming stable, and that if your are targeting the spike, it is not a protein that will vanish in a few months. That is good news.” The bad news, he says, is that they have also identified 27 amino acids on the virus’s 29 proteins as places that are still changing a lot.

“These are all ways the virus will have to avoid targeting by the vaccines we may be generating.”

You see, in addition to copying errors, viruses mutate after hitting roadblocks, and the new vaccines will create a barrier to function as the spike protein comes under attack. Though it may look like an Achilles heel crucial to COVID-19’s survival, “the S protein is just one entry point of the many things occuring with the infection process,” he says. “Without it, the titer of the virus will decrease, but the virus will continue to infect.”

If anything, the lesson of COVID-19’s ongoing mutation, a story now writing it’s second and third chapters, may be that we will be lucky if our vaccines provide us with a bridge to normalcy until the next mutation that matters.

In this sense, the end goal of COVID-19 genetic tracking becomes not so much the eradication of the virus, but staying on top of the changes long enough for the body to knock it back into something more manageable.

“Some coronaviruses live with us and do not cause disease,” Caetano-Anolles says. “That’s the best option for the virus … It wants to strike a balance between very aggressive and very mild. This thing came from animals, so it is an oddity, and is trying to reach that equilibrium.”

Caetano-Anolles is reluctant to predict how long that could take. We have, he says, opened Pandora’s box.

Viruses are part of the cycle of life. Like cancer, they are products of mutation, something that presumably promotes adaptation, diversity and survival. It suggests we will find a path to coexistence with SARS-CoV-2.

“Humans, animals and all organisms have been living with viruses for a long time … this pandemic is just highlighting that,” he says.

These are pretty big subjects for a team of grad students.

“We were lucky,” he says, “to ask interesting questions about how the virus is changing in the first wave that went through the world. We need to ask these questions of second and third wave now upon us.”

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