Transmission electron microscope image of SARS-CoV-2, the virus that causes Covid-19.
Source: BSIP / Universal Images Group / Getty Images
Source: BSIP / Universal Images Group / Getty Images
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Then Bette Korber, a biologist from Los Alamos National Laboratory, spotted the first significant mutation in the Covid-19 virus last spring, some scientists were skeptical. They did not believe that it would make the virus more contagious and said that its rapid rise could only be accidental.
Now, 11 months later, the D614G mutation she’s helped discover is worldwide, appears in the genomes of rapidly spreading varieties from the United Kingdom, South Africa and Brazil. Meanwhile, new mutations are emerging in increasingly complex patterns, prompting biologists to push for new ways of detecting a fire hose from incoming genomic data.
The goal: to quickly discover variants that could reduce the effectiveness of vaccines for a pathogen that are unlikely to be eradicated any time soon. The SARS-CoV-2 virus can go down and become a nuisance just like the common cold. Or, like flu, it can retain the ability to cause serious illness in some population segments, a scenario that may require regular boosters.
Source: Los Alamos National Lab
‘If we keep a close eye on it, we can stay ahead of the virus and that’s what everyone is skarrel to do now, ”says Korber, who is creating new mathematical tools to detect medically important variants.
The flood of new genome data is so great that the Los Alamos laboratory had to upgrade its servers to handle the incoming data. Meanwhile, Korber is on four Zoom calls a week with experts worldwide to design criteria to decide when mutations are enough to earn detailed follow-up from labs on how they could affect the vaccines.
An important mystery that the best scientists learned early on was what kind of virus the coronavirus would be. So far, it looks more like flu, which is constantly formative and needs annual vaccination, than measles, a virus that is so intolerant to mutation that one vaccine system lasts a lifetime.
“Does that mean we have to make a new vaccine every year?” said Paul Duprex, who heads the University of Pittsburgh’s Center for Vaccine Research. “We do not know.”
First, mRNA vaccines for Covid-19 have efficacy rates of over 90%, much higher than the 60% for flu shots in a good year. But vaccine manufacturers Moderna Inc. and Pfizer Inc., with its partner BioNTech SE takes no chances. In case they are already starting trials with booster shots aimed at B.1.351, the antibody-evading strain that was first spotted in South Africa.
When viruses replicate and copy their genomes, errors can trigger the long string of RNA or DNA “letters” that determine how viral proteins are developed. Many of the bugs have no effect, or it may even make the virus less suitable. But a small percentage of these changes can give the virus a head start, making it more contagious or evading the immune system.
The HIV virus is notorious for its rapid mutation rate. In comparison, SARS-CoV-2 mutates at a much slower rate, in part due to a proof-reading enzyme that limits changes. But with more than 125 million infections worldwide, some bugs are likely to slip through.
At the same time, the virus has found cunning ways to avoid the proofreading mechanism, University of Pittsburgh researchers found. Instead of making changes to individual RNA letters, groups of different letters are removed simultaneously, which apparently undermines the ability of the virus’ natural spell-testing systems to detect the change.
74-day Bout
Some of the first scratches were seen in an immune-deficient cancer patient being treated at the University of Pittsburgh Medical Center, who died after a 74-day attack with Covid-19. Over time, according to the University of Pittsburgh’s Duprex, several immune escape shakes developed, which reported in November on the removal of the cancer patient.
“If the damn thing is gone, you will not be able to fix it,” Duprex said.
What makes the future of SARS-CoV-2 so difficult to predict is that viral evolution is like a three-dimensional chess game. It is not only the individual mutations that matter, but also the order and combinations in which they occur. According to Mark Zeller, a scientist from the United States, a single mutation can subtly alter the virus and alter the impact of others. Scripps Research Institute in San Diego.
Shared mutations
Both the B.1.351 strain that is common in South Africa, and the P.1 strain that infects Brazil, share different mutations in the peak protein that the virus uses to gain access to cells. These include the D614G mutation discovered by Korber, which makes the peak more stable, and the E484K mutation, which presumably reduces the ability of some antibodies to bind to the peak.
For reasons not yet fully understood, it is so far the B.1.351 that appears to have more impact on Pfizer and Moderna vaccines, at least in laboratory tests.
Overall, the record for eliminating viruses was weak, with smallpox being the prime example. Even polio bags are still in some countries, despite efforts to eliminate them. According to the current virus, this does not bode well for the current virus. Jesse Bloom, a researcher at the Fred Hutchinson Cancer Research Center studying viral evolution.
“Vaccination is going to take down the pandemic in a very significant way,” Bloom said. “But I do not think we are going to eradicate SARS-CoV-2.”
Bloom predicts that it will “take a number of years” before the virus acquires enough mutations to completely escape existing vaccines. Of the approximately 100,000 possible single letter mutations for the virus, less than 1% are likely to help the virus evade antibodies. .
A hopeful scenario
Although the virus continues to develop in the short term, one of the most hopeful scenarios is that the major moves it could make could be to evade antibodies that make the current vaccinations work. In this scenario, there is a practical limitation on how much the virus can mutate and remain fit to invade our cells.
According to Shane Crotty, a researcher at the La Jolla Institute of Immunology, the ear protein must retain a form that can bind it effectively to its human receptor.
“There are not an infinite number of possibilities,” he said. ‘It’s like putting your foot in a shoe. It should still have basically the right shape and size and should still be recognized as a shoe. ‘
Nevertheless, evidence from other cold coronaviruses indicates that they may mutate to evade the immune system over time.
In a recent study, Bloom and his colleagues compared the 1984 version of a common cold coronavirus called 229E with a version of the same strain that spread in 2016, three decades later. A total of 17% of the RNA letters in an important part of the ear protein that binds the virus to cells have been exchanged due to mutations.
To test what it means for human immunity, they obtained patient blood samples from the 1980s that could neutralize the 1984 viral strain. These people were probably exposed to the 1984 virus and developed protective antibodies against it.
Faded protection
When the researchers tested the samples against strains of the 229E virus that appeared in the 1990s or later, the protection faded: only 2 out of 8 blood samples were able to neutralize the 2016 strain, and the two showed a greatly reduced activity versus the most recent virus.
This gives some tips for the amount that may change in the future, given enough time. “It’s pretty clear that human coronaviruses are undergoing significant antigenic evolution,” Bloom said in an interview.
However, it remains unknown whether the virus can retain the ability to cause serious diseases as it mutates and more people gain immunity through infections or vaccinations.
In research published in the journal Science in January, disease modelers at According to Emory University, the most important factor or protection against serious diseases is significantly longer lasting than protection against mild or asymptomatic reinfections, something that is typical of coronaviruses that cause colds.
While the study was done before the current variant emerged, its basic conclusions hold, according to Jennie S. Lavine, a postdoctoral researcher at Emory University.
“What we see with Covid-19 on a molecular and cellular level is not in line with what we see with endemic coronaviruses,” Lavine said. “Immunity is declining, but not everything is waning fast.”