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Coronavirus is changing: the Washington Post




Health workers from the University of South Florida Health administer coronavirus tests on June 25 in a community center in Tampa. (Octavio Jones / Getty Images)

When the first Coronavirus cases in Chicago appeared in January, bearing the same genetic signatures as a germ that emerged in China weeks earlier.

But while Egon Ozer, an infectious disease specialist from Northwestern University’s Feinberg School of Medicine, was examining the genetic structure of virus samples from local patients, he noticed something different.

A change in the virus was appearing again and again. This mutation, associated with outbreaks in Europe and New York, eventually conquered the city. In May, it was found in 95 percent of all Ozer-sequenced genomes.

At first glance, the mutation seemed trivial. About 1,300 amino acids act as building blocks for a protein on the virus surface. In the mutant virus, the genetic instructions for only one of those amino acids – number 614 – have changed in the new variant from a “D” (short for aspartic acid) to a “G” (short for glycine).

But the position was significant, because the passage took place in the part of the genome that codes for the very important “spike protein” – the protruding structure that gives the coronavirus its crown profile and allows it to enter human cells as a thief chooses a door lock.

And its ubiquity is undeniable. Of the approximately 50,000 genomes of the new virus that researchers around the world have uploaded to a shared database, about 70 percent carry the mutation, officially designated D614G but better known by scientists as “G.”

The small mutation found in

dominant variant of coronavirus

Like all coronaviruses, SARS-CoV-2 has a series of characteristic peaks that surround its core. These spikes are what allow the virus to attach itself to human cells.

A mutation affecting the peak virus protein changed the amino acid 614 from “D” (aspartic acid) to “G” (glycine). Research suggests that this small change – affecting three identical amino acid chains – could make the peak protein more effective, improving virus infectivity.

Source: GISAID, Post reporting

AARON STECKELBERG / THE WASHINGTON POST

The small mutation found in

dominant variant of coronavirus

Like all coronaviruses, SARS-CoV-2 has a series of characteristic peaks that surround its core. These spikes are what allow the virus to attach itself to human cells.

A mutation affecting the peak virus protein changed the amino acid 614 from “D” (aspartic acid) to “G” (glycine). Research suggests that this small change – affecting three identical amino acid chains – could make the peak protein more effective, improving virus infectivity.

Source: GISAID, Post reporting

AARON STECKELBERG / THE WASHINGTON POST

The small mutation found in

dominant variant of coronavirus

Like all coronaviruses, SARS-CoV-2 has a series of characteristic peaks that surround its core. These spikes are what allow the virus to attach itself to human cells.

A mutation affecting the peak virus protein changed the amino acid 614 from “D” (aspartic acid) to “G” (glycine). Research suggests that this small change – affecting three identical amino acid chains – could make the peak protein more effective, improving virus infectivity.

Source: GISAID, Post reporting

AARON STECKELBERG / THE WASHINGTON POST

The small mutation found in

dominant variant of coronavirus

Like all coronaviruses, SARS-CoV-2 has a series of characteristic peaks that surround its core. These spikes are what allow the virus to attach itself to human cells.

A mutation affecting the peak virus protein changed the amino acid 614 from “D” (aspartic acid) to “G” (glycine). Research suggests that this small change – affecting three identical amino acid chains – could make the peak protein more effective, improving virus infectivity.

Source: GISAID, Post reporting

AARON STECKELBERG / THE WASHINGTON POST

The small mutation found in

dominant variant of coronavirus

Like all coronaviruses, SARS-CoV-2 has a series of characteristic peaks that surround its core. These spikes are what allow the virus to attach itself to human cells.

A mutation affecting the peak virus protein changed the amino acid 614 from “D” (aspartic acid) to “G” (glycine). Research suggests that this small change – affecting three identical amino acid chains – can make the peak protein more effective, improving the infectivity of the virus.

Source: GISAID, Post reporting

AARON STECKELBERG / THE WASHINGTON POST

“G” didn’t just dominate the Chicago epidemic – it took over the world. Now scientists are running to understand what it means.

At least four laboratory experiments suggest that the mutation makes the virus more contagious, although none of these works have been peer reviewed. Another unpublished study conducted by scientists from the Los Alamos National Laboratory says that patients with the G variant actually have more viruses in their bodies, making them more likely to spread it to others.

The mutation doesn’t seem to make people sicker, but a growing number of scientists fear it has made the virus more contagious.

“The epidemiological study and our data together really explain why [G variant’s] the spread in Europe and the United States has been very rapid, “said Hyeryun Choe, a virologist at Scripps Research and lead author of an unpublished study on the greater infectivity of the G variant in laboratory cell cultures.” This is not just random. “

But there could be other explanations for the variant G domain: distortions in which genetic data are collected, temporal oddities that have given the mutated virus an early foothold in sensitive populations.

“The bottom line is that we haven’t seen anything definitive yet,” said Jeremy Luban, a virologist at the University of Massachusetts at Amherst.

The struggle to unravel this mutation mystery embodies the challenges of science during the coronavirus pandemic. With millions of infected people and thousands of people dying every day all over the world, researchers must find a high balance between getting information quickly and making sure it is right.

The mutation of the Spike protein takes over

A mutation in the SARS-CoV-2 virus peak protein changes only one amino acid in a chain of around 1,300, but it could make a difference in how the virus attacks human cells. The mutation (called D614G), which first appeared in January, is found in what has become the dominant variant of the coronavirus.

New weekly samples

in the global sub-sample of Nextrain

Proportion of samples with the D614G mutation

Proportion of samples without

the D614G mutation

The data includes 3,006 samples acquired on June 24.

Source: Nextstrain, GISAID

JOE FOX / THE WASHINGTON POST

The mutation of the Spike protein takes over

A mutation in the SARS-CoV-2 virus peak protein changes only one amino acid in a chain of around 1,300, but it could make a difference in how the virus attacks human cells. The mutation (called D614G), which first appeared in January, is found in what has become the dominant variant of the coronavirus.

New weekly champions in the Nextrain global sub-sample

Proportion of samples with the D614G mutation

Proportion of samples without

the D614G mutation

The data includes 3,006 samples acquired on June 24.

Source: Nextstrain, GISAID

JOE FOX / THE WASHINGTON POST

The mutation of the Spike protein takes over

A mutation in the SARS-CoV-2 virus peak protein changes only one amino acid in a chain of around 1,300, but it could make a difference in how the virus attacks human cells. The mutation (called D614G), which first appeared in January, is found in what has become the dominant variant of the coronavirus.

New weekly champions in the Nextrain global sub-sample

Proportion of samples with the D614G mutation

Proportion of samples without D614G mutation

The data includes 3,006 samples acquired on June 24.

Source: Nextstrain, GISAID

JOE FOX / THE WASHINGTON POST

The mutation of the Spike protein takes over

A mutation in the SARS-CoV-2 virus peak protein changes only one amino acid in a chain of around 1,300, but it could make a difference in how the virus attacks human cells. The mutation (called D614G), which first appeared in January, is found in what has become the dominant variant of the coronavirus.

New weekly champions in the Nextrain global sub-sample

Proportion of samples with the D614G mutation

Proportion of samples without D614G mutation

The data includes 3,006 samples acquired on June 24.

JOE FOX / THE WASHINGTON POST

Source: Nextstrain, GISAID

A better choice of block

SARS-CoV-2, the new coronavirus that causes covid-19 disease, can be considered an extremely destructive thief. Unable to live or reproduce alone, he breaks down into human cells and co-opt their biological machinery to make thousands of copies of himself. This leaves a trail of damaged tissue and triggers an immune system response which can be disastrous for some people.

This replication process is messy. Although it has a “proofreading” mechanism to copy its genome, the coronavirus often makes mistakes or mutations. The vast majority of mutations have no effect on virus behavior.

But since the virus genome was first sequenced in January, scientists have been looking for significant changes. And few genetic mutations could be more significant than those affecting the spike protein – the virus’ most powerful tool.

This protein attaches to a receptor on respiratory cells called ACE2, which opens the cell and lets the virus slip inside. The more effective the spike protein, the more easily the virus can penetrate the bodies of its hosts. Even when the original variant of the virus emerged in Wuhan, China, it was evident that the peak protein on SARS-CoV-2 was already effective enough.

SARS-CoV-2 uses its peak to bind to the ACE2 receptor, allowing access to the cell.

The virus RNA is released into the cell. The cell reads RNA and makes proteins.

Proteins are assembled into new copies of the virus, which then infect multiple cells.

AARON STECKELBERG / THE WASHINGTON POST

SARS-CoV-2 uses its peak to bind to the ACE2 receptor, allowing access to the cell.

The virus RNA is released into the cell. The cell reads RNA and makes proteins.

Proteins are assembled into new copies of the virus, which then infect multiple cells.

AARON STECKELBERG / THE WASHINGTON POST

The virus RNA is released into the cell. The cell reads RNA and makes proteins.

Proteins are assembled into new copies of the virus, which then infect multiple cells.

SARS-CoV-2 uses its peak to bind to the ACE2 receptor, allowing access to the cell.

AARON STECKELBERG / THE WASHINGTON POST

SARS-CoV-2 uses its peak to bind to the ACE2 receptor, allowing access to the cell.

The virus RNA is released into the cell. The cell reads RNA and makes proteins.

Proteins are assembled into new copies of the virus, which then infect multiple cells.

AARON STECKELBERG / THE WASHINGTON POST

But it could have been even better, said Choe, who studied peak proteins and how they bind to the ACE2 receptor since the acute respiratory syndrome epidemic in 2003.

The peak protein for SARS-CoV-2 has two parts that do not always hold well together. In the version of the virus that emerged in China, Choe said that the external part – which the virus must attach to a human receptor – often stopped. Equipped with this defective pick, the virus had difficulty invading host cells.

“I think this mutation managed to compensate,” Choe said.

By studying both versions of the gene using a proxy virus in a petri dish of human cells, Choe and his colleagues found that viruses with the G variant had more peak proteins and that the outer parts of those proteins had less likely to break. This made the virus about 10 times more infectious in the laboratory experiment.

The mutation does not appear to lead to worse results in patients. Nor did it alter the virus’s response to the antibodies of patients who had variant D, Choe said, suggesting that vaccines developed based on the original version of the virus will be effective against the new strain.

Choe uploaded a manuscript describing this study on the BioRxiv website, where scientists can publish “prepress” research that has not yet been peer-reviewed. He also sent the document to an academic journal, which has not yet published it.

The peculiar infectivity of the variety G is so strong that scientists were attracted to the mutation even when they weren’t looking for it.

Neville Sanjana, geneticist from the New York Genome Center and New York University, was trying to figure out which genes allowed SARS-CoV-2 to infiltrate human cells. But in experiments based on a genetic sequence taken from a first case of the virus in Wuhan, he struggled to get that form of the virus to infect cells. Then the team switched to a model virus based on the variant G.

“We were shocked,” said Sanjana. “Here! It was just this huge increase in viral transduction.” They repeated the experiment in many cell types and each time the variant was many times more contagious.

Their findings, published as prepress on BioRxiv, generally corresponded to what Choe and other laboratory scientists were seeing.

But the New York team offers a different explanation as to why the variant is so contagious. Considering that Choe’s study suggests that the mutation has made the spike protein more stable, Sanjana said that experiments over the past two weeks, not yet made public, suggest that the improvement is actually in the infection process. He hypothesized that the G variant is more efficient at the beginning of the process of invading the human cell and acquiring its reproductive system.

Luban, who also experimented with the D614G mutation, was attracted to a third possibility: his experiments suggest that the mutation allows the peak protein to change shape as it attaches to the ACE2 receptor, improving its ability to merge with the host cell. .

Several approaches to making their virus model could account for these discrepancies, Luban said. “But it is quite clear that something is happening.”

Unanswered questions

Although these experiments are compelling, they are not conclusive, said Kristian Andersen, a Scripps virologist not involved in any of the studies. Scientists need to understand why they identified different mechanisms for the same effect. All studies have yet to pass peer review and must be reproduced using the real version of the virus.

Even then, Andersen said, it will be too early to say that the G variant transmits faster among people.

Cell culture experiments have previously been flawed, noted Anderson Brito, a computational biologist at Yale University. Early experiments with hydroxychloroquine, a malaria drug, hinted that it was effective in fighting coronavirus in a petri dish. The drug was touted by President Trump and the Food and Drug Administration authorized it for emergency use in hospital patients 19. But that authorization was revoked this month after tests showed that the drug was ” unlikely to be effective “against the virus and presented potential security risks.

So far, the largest transmission study has come from Bette Korber, a computational biologist from the Los Alamos National Laboratory who has built one of the world’s largest viral genome databases for monitoring HIV. In late April, she and colleagues from Duke University and the University of Sheffield in Great Britain published a draft of their work claiming that the mutation increases the transmission of the virus.

Analyzing sequences from over two dozen regions around the world, they found that most places where the original virus was dominant before March were eventually detected by the mutated version. This passage was particularly evident in the United States: ninety-six percent of the first sequences here belonged to the D variant, but at the end of March nearly 70 percent of the sequences carried the amino acid G instead.

British researchers also found that people with the G variant had multiple viral particles in their bodies. Although this higher viral load doesn’t seem to make people sicker, it could explain the rapid spread of the G variant, scientists wrote. People with multiple viruses to be eliminated are more likely to infect others.

The Los Alamos project drew intense scrutiny when it was released in the spring and many researchers remain skeptical of its conclusions.

“There are so many biases in the data set here that you can’t check and you may not know they exist,” said Andersen. At a time when 90 percent of U.S. infections are still undetected and countries with limited healthcare infrastructure are struggling to keep up with rising cases, a data shortage means “we can’t answer all the questions we want to answer. . “

Pardis Sabeti, computational biologist of Harvard University and the Broad Institute, observed that the vast majority of the sequenced genomes come from Europe, where the G variant first emerged, and from the United States, where it is believed that infections were introduced by travelers from Europe unnoticed for weeks before the country closed. This could at least partially explain why it seems so dominant.

The success of the mutation could also be a “founding effect,” he said. Getting to a place like Northern Italy – where the vast majority of sequenced infections are caused by the variant G – found an easy purchase in an older and largely unprepared population, which then unwittingly spread it far and wide .

Scientists may be able to rule out these alternative explanations with more rigorous statistical analyzes or a controlled experiment in an animal population. And as studies on the D614G mutation pile up, researchers are beginning to convince itself of its significance.

“I think we’re slowly starting to reach consensus,” said Judd Hultquist, a virologist from Northwestern University.

Solving the mystery of the D614G mutation won’t make much difference in the short term, Andersen said. “We haven’t been able to deal with D,” he said. “If G transmits even better, we won’t be able to handle it.”

But it’s still essential to understand how the genome affects the behavior of the virus, scientists say. Identifying emerging mutations allows researchers to trace their spread. Knowing which genes influence the way the virus transmits allows public health officials to adapt their efforts to contain it. Once therapy and vaccines are distributed on a large scale, having a basic understanding of the genome will help pinpoint when drug resistance begins to evolve.

“Understanding how the broadcasts are taking place will not be a magic bullet, but will help us respond better,” said Sabeti. “This is a race against time.”


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