A New Coronavirus Mutation Is Taking Over The World

August 19, 2020

A mutation in the protein that allows SARS-CoV-2 to enter cells may make it easier for the virus to spread – or it may make no difference at all.

That’s the crux of the controversy over the mutation known as D614G, which affects spiking proteins on the surface of the virus. The mutation is not new. It appears in low-level samples taken from COVID-19 patients as early as February. But this mutation of the virus (nicknamed the “G” mutation) appears to show up in more and more samples of the virus taken from infected people recently compared to earlier in the pandemic.

A new paper published July 2 in the journal Cell argues that the rise in the neo-coronavirus “G” variant is due to natural selection. The study found that viral particles with this mutation enter cells more easily, suggesting that it is overtaking other strains of the virus to become the dominant version of SARS-CoV-2. Other experiments that have not yet been published have found similar results. However, some researchers are not yet convinced that the mutation has any real effect on the spread of the coronavirus. Rather, it’s possible that the G variant spreads by chance, says Nathan Grubaugh, an epidemiologist at Yale School of Medicine who co-authored a review that accompanied the paper.

“The virus could easily get lucky,” Grubaugh told Live Science.

G vs. D
The original sample of the new coronavirus out of Wuhan, China, was a mutation that scientists now call the “D” clade. Before March 1, more than 90 percent of the virus samples collected from patients were from this “D” clade variant. During the course of March, the G began to predominate. This mutation is caused by the exchange of adenine (A) nucleotides for guanine (G) nucleotides at a specific location in the coronavirus genome. It always occurs along with three other mutations that also swap one building block of RNA for another. (The letters in RNA help encode proteins made by the virus inside the cell).

The G mutation represented 67 percent of the global sample in March and 78 percent of the sample between April 1 and May 18. During that time, the outbreak shifted from China to Europe and the United States.

The mutation drew interest because it seemed to take over even in areas where the D mutation was initially held around, said Bette Korber, lead author of the new cell paper and a computational biologist at Los Alamos National Laboratory in New Mexico. She and her colleagues at Duke University and the La Jolla Institute for Immunology in California inserted the G and D mutations into pseudoviruses, which are viruses designed to display surface proteins of other viruses.Korber told Live Science that pseudoviruses are useful because they can’t spread disease and because they contain molecular tags that researchers can use to track their entry into cells’ movement.

The researchers then exposed cell cultures to pseudoviruses with coronavirus spiking protein G or D variants to track which virus was more infectious. They found that the G variant resulted in higher viral loads in the cell cultures, indicating increased infection and replication. The viral load found from the G variant of the spike protein was 2.6 to 9.3 times greater than that found from the D variant of the spike protein.

The sham viruses and cells used in the experiment were neither true coronaviruses nor human lung cells, but another study using the infectious SARS-CoV-2 virus came to similar conclusions. That study, published July 7 in the preprint server bioRxiv and not yet peer-reviewed, was led by biologist Neville Sanjana of New York University. He and his colleagues tested the G and D versions of SARS-CoV-2 in cell cultures, including human lung cells, and found that the G variant infected eight times as many cells as the D variant.

But just because a virus is better at infecting cells in laboratory cultures doesn’t mean it’s going to spread more easily in the real world, Grubaugh said.” If it just takes it [a few] more hours for another variant to do the exact same thing, then the result is essentially the same,” he told Live Science. and getting into cells is only part of the equation. There are many factors that affect transmissibility, he said, such as how efficiently the virus leaves the body and how stable it is in the external environment as it waits for a new host.

Some clinical work suggests that the distinct advantage of the G variant may be maintained outside of the petri dish.A study published May 26 in the preprint database medRxiv, which also has not yet been peer-reviewed, led by Northwestern University Feinberg School of Medicine researchers Dr. Egon Ozer, Judd Hultquist, found that SARS in circulation in Chicago in mid-March -CoV-2 has three different versions. Some match the dominant version circulating in New York City, some match the dominant version on the West Coast, and some seem to be most closely related to the original sample from China.

“The virus kind of went around both sides of the globe and hit Chicago, and the virus we got originally came from China, and we think that’s due to O’Hare being such a transportation hub,” Hultquist told Live Science.

The researchers found that the New York clade containing the G mutation was associated with a higher viral load in the upper respiratory tract, rather than a virus closer to the original Chinese strain. Researchers in Washington State have published similar findings. If the results hold, they could suggest increased transmission because higher levels of virus in the upper respiratory tract could translate into more virus emitted when people breathe and speak, Ozell told Live Science. But it’s impossible to say for sure, he said. Scientists don’t even know how much virus a person needs to be exposed to in order to be infected, so it’s unclear whether the extra viral load makes a difference.

The lucky break?
It’s possible that the G mutation in the coronavirus spiking protein is, indeed, giving it some sort of transmissibility advantage over other strains of the virus, Grubaugh says. But it hasn’t been proven yet.The G mutation could also be taking over the world purely by luck, rather than by evolutionary adaptation. That’s due to something epidemiologists call the “founder” effect.

“If this virus gets into a population with a lot of connectivity, essentially like a super-transmitter event, it can spread very quickly just because that’s the founder of that population,” Grubaugh says.

What does this do for the G mutation? The strain was lucky to land in Europe, where a massive outbreak infected many people. From there, it got even luckier, landing in New York City, the center of global networking. The outbreak in New York planted the seeds for many outbreaks in other parts of the United States, including many places where the virus now runs largely unchecked.

“The most important thing now is to continue monitoring in those places,” Grubaugh said. If the G variant continues to predominate, even in places where both G and D versions are present, it could be a sign that the G mutation does indeed provide a transmission advantage for the virus.

The G614 mutation is part of a cluster of four mutations that appeared together, Korber said, so more work needs to be done on what the other three mutations might do. Another important piece of work will be to test genetic variations in animal models to better simulate human transmission. Scientists are working with a number of animals, from ferrets to Syrian hamsters to rhesus monkeys, to study coronaviruses, but they have yet to determine which animals best represent how the disease spreads from human to human. (Hamsters and ferrets get infected with the flu much like humans do, so scientists hope they might also be good animal models for coronavirus transmission).

The good news, the researchers agree, is that so far there is no evidence that the G mutation causes more severe disease than any other version of the coronavirus, nor do the mutations seem likely to affect the progress of vaccine development. But the findings suggest that it’s important for scientists to track mutations in the virus as it spreads. As the virus interacts with more and more of the immune system, it will undergo more evolutionary pressure and may continue to change, Ozell said.

“We’ve seen that in a month’s time, a particular form of the virus can go from a very rare form to the most common form globally,” Korber said.” It could happen again.”

For the general public, the advice hasn’t changed: Social distancing and wearing masks remain best practices after a lockdown, Korber said. The mutation is here to stay, Grubaugh said, and what it does to the virus may be more important now than what people do.

“There are a lot of other more important things to worry about right now than this mutation,” he said.” We can’t even get the tests right, we really don’t have effective control measures at all right now…. If we keep allowing the virus the opportunity to have a new host, it’s going to keep spreading, whether it’s a more suitable variant or not.”