It is possible that the ancestors of the new coronavirus circulated in bats unnoticed for decades. And it is that these coronaviruses could also infect humans, according to a new study.
To understand where the novelty of coronavirus, known as SARS-CoV-2, came from, and how it spread to humans, scientists must trace its evolutionary history through the virus’s genes, encoded in ribonucleic acid or RNA. But the evolutionary history of SARS-CoV-2 is complicated, because coronavirus They are known to exchange frequently genetic material with other coronaviruses.
This change in genes, called genetic recombination, also causes scientists to find out how coronavirus first spread to humans; some researchers propose a direct transmission of the bat to man, while others propose that an average species existed, such as pangolins, involved.
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In the new study, researchers first identified the RNA sections of the SARS-CoV-2 genome that had been evolving “as a whole piece,”; without genetic recombination, to the point that they could study, he said. co-lead author Maciej. Boni, associate professor of biology at the Penn State Center for Infectious Disease Dynamics.
They then compared these genetic regions with those of bat and pangolin-like coronaviruses. Adding evidence to support previous findings, they found that SARS-CoV-2 was more closely related to another bat coronavirus, known as RaTG13.
In previous studies, scientists had specifically studied the genes responsible for the so-called coronavirus receptor binding domain (RBD). “ear” protein – the piece that allows the virus to dock the ACE2 receptor on human cells and infect them. The research found that the RBD portion of the spike protein was genetically more similar to a coronavirus found in pangolins (called Pangolin-2019) than that of RaTG13. There are two possible explanations for this finding: first, that the SARS-CoV-2 virus had evolved its ability to spread to humans in pangolins (it is unlikely, since SARS-CoV-2 is more closely related). with RaTG13 than known pangolin viruses). ), or the second, that SARS-CoV-2 had acquired this RBD by recombination with a pangolin virus, Boni said.
But in the new analysis, the researchers found no evidence of recombination in the SARS-CoV-2 ear protein genes. In contrast, new genetic sequencing data suggest a third explanation for what happened: The genes for the ear protein, and therefore the coronavirus’s ability to infect human cells, were transmitted from a common ancestor. which resulted in all three coronaviruses: SARS-CoV-2, RaTG13, and Pangolin-2019.
The authors note that it is still possible that the pangolins “or another hitherto undiscovered species” may have acted as an intermediate host that helped the virus spread to humans. But “it’s unlikely,” Boni said. Rather, new findings suggest that the ability of both humans and pangolins to replicate in the upper airways evolved in bats. From bats, SARS-CoV-2 could have spread directly to humans.
Circulating for decades
But when did the lineage that gave rise to SARS-CoV-2 first differentiate itself from the other two virus lineages? To find out, the researchers identified mutations or differences in specific nucleotides, the molecules that make up coronavirus RNA, between different viruses. They then counted the number of mutations present in regions of the SARS-CoV-2 genome that had not been recombined. And knowing the estimated rate at which the coronavirus changes each year, they calculated how much time has passed since they diverged.
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They found that more than a century ago, there was a single lineage that would eventually give rise to SARS-CoV-2, RaTG13 and Pangolin-2019 viruses. Even then, “this lineage probably had everything it needed amino acids “Boni said their amino acids are the building blocks proteins such as ear protein).
The Pangolin-2019 virus then deviated from the SARS-CoV-2 and RaTG13 viruses. Then, in the 1960s or 1970s, this lineage split in two, creating the RaTG13 lineage and the SARS-CoV-2 lineage. Sometime between 1980 and 2013, the RaTG13 lineage lost its ability to bind to the human receptor, but SARS-CoV-2 did not.
“The SARS-CoV-2 lineage circulated in bats for 50 or 60 years before jumping into humans,” Boni said. Near the end of 2019, “someone had just had a lot of bad luck” and contacted SARS-CoV-2 and scored a pandemic.
There are probably other virus lineages of the same centennial ancestor that also underwent decades of evolution, “which we don’t quite characterize,” Boni said. “The question is,‘ Are there half a dozen of these lineages, 20 or a hundred? “- and no one knows.” But there are likely to be other people hiding in bats who are able to spread to humans, he said.
“This article provides more clues to understanding how this and other coronaviruses may arise,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Health Security Center in Baltimore, who was not part of the study. “We only know the tip of the iceberg when it comes to viruses that have bat prison.” Seeing that coronavirus relatives have been around for so many years suggests that there are not so many examples. “When it comes to pandemic preparedness, having a much more robust surveillance system is really the only way to protect against these threats in the future,” Adalja said.
Boni shows virus sampling in domestic and wild birds in East Asia, Southeast Asia and other parts of the world to try to prevent possible bird flu pandemics. “If someone gets infected with a grandfather grip virus, the time back to understand that it would be like 48 hours, and we would immediately know that this person should be isolated right away and other measures would follow. “But for coronaviruses, there are no such preventive measures,” he added.
It was more than a month after SARS-CoV-2 first spread to humans so that scientists had the new coronavirus genome in their hands, long enough for the virus to spread to a thousand people. , said Boni. “By then it was too late.”
The findings were published in the journal on July 28 Microbiology of nature.
Originally published in Live Science.