The ancestors of the new coronavirus may have been circulating in undetected bats for decades. And those coronaviruses probably also had the ability to infect humans, according to a new study.
To understand where the new coronavirus, known as SARS-CoV-2, comes from, and how it spread to humans, scientists need to trace its evolutionary history through the virus’s genes, which are encoded in ribonucleic acid or RNA. But the evolutionary history of SARS-CoV-2 is complicated, because coronavirus are known to exchange frequently genetic material with other coronaviruses.
That gene exchange, called genetic recombination, also makes it difficult for scientists to determine how the coronavirus first spread to humans; some researchers propose a direct transmission from bat to human, while others hypothesize that there was a medium species, such as pangolininvolved
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In the new study, researchers first identified RNA sections in the SARS-CoV-2 genome that had been evolving “as a whole piece”, without genetic recombination, since they were able to study, said co-author Maciej Boni. , an associate professor of biology at the Penn State Center for Infectious Disease Dynamics.
They then compared these genetic regions with those of similar coronaviruses found in bats and pangolins. By adding evidence to back up 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 looked at genes responsible for the so-called coronavirus receptor binding domain (RBD) “spike” protein – the piece that allows the virus to couple to the ACE2 receptor in human cells and infect them. That 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 developed its ability to spread to humans in pangolins (unlikely, given that SARS-CoV-2 is more closely related to RaTG13 than any virus known pangolin)), or 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 genes for the SARS-CoV-2 tip protein. Instead, the new genetic sequencing data suggests a third explanation for what happened: the spike protein genes, and thus the coronavirus’s ability to infect human cells, were passed down from a common ancestor that eventually gave rise to the three coronaviruses: SARS-CoV-2, RaTG13 and Pangolin-2019.
The authors note that it is still possible that pangolins “or another hitherto undiscovered species” may have acted as an intermediate host that helped the virus spread to humans. But “it is unlikely,” Boni said. Conversely, the new findings suggest that the ability to replicate in the upper respiratory tract of both humans and pangolins actually evolved in bats. Of the bats, SARS-CoV-2 could have spread directly to humans.
Hanging around for decades
But when did the lineage that gave rise to SARS-CoV-2 deviate from the other two virus lineages? To solve this, the researchers identified mutations or differences in specific nucleotides, the molecules that make up the coronavirus RNA, among the different viruses. They then counted the number of mutations present in the SARS-CoV-2 genome regions that had not been recombined. And knowing the estimated rate at which the coronavirus mutates each year, they calculated how long it had been since the three diverged.
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They discovered that over a century ago, there was a unique lineage that would eventually give rise to the SARS-CoV-2, RaTG13, and Pangolin-2019 viruses. Even then, “this lineage probably had everything necessary amino acids at its receptor binding site to infect human cells, “Boni said. (Amino acids are the building blocks of protein like spike protein).
At that time, the Pangolin-2019 virus diverged from the SARS-CoV-2 and RaTG13 viruses. Then, in the 1960s or 1970s, this lineage split into 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 to 60 years before jumping to humans,” Boni said. Near the end of 2019, “someone just had bad luck” and came into contact with SARS-CoV-2 and that triggered a pandemic.
There are likely other virus lineages of the same centennial ancestor that also underwent decades of evolution, “which we simply have not characterized,” Boni said. “The question is: ‘Are there half a dozen of these lineages, 20 or a hundred?’ – and nobody knows. ” But there are likely others hidden in bats that can spread to humans, he said.
“This document provides further clues to understanding how this and other coronaviruses can arise,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Safety in Baltimore, who was not part of the study. “We only really know the tip of the iceberg when it comes to the viruses found in bats.” Seeing that the relatives of the coronavirus have existed for so many years, he suggests that there are many samples. “When it comes to pandemic preparedness, having a much more robust surveillance system is really the only way to protect ourselves against these threats in the future,” said Adalja.
Large numbers of virus samples are performed on domestic and wild birds in East Asia, Southeast Asia and other parts of the world in an effort to prevent possible avian flu pandemics, Boni said. “If someone gets infected with an avian influenza virus, the response time to understand that it would be something like 48 hours and we would immediately know that this person needs to be isolated immediately and that other measures would follow “. But for bat coronaviruses, there are no such preventive measures, he added.
It took more than a month after SARS-CoV-2 first spread to humans for scientists to have the new coronavirus genome on their hands, long enough for the virus to have spread to thousands of people, Boni said. “At that time it was too late.”
The findings were published July 28 in the journal. Microbiology nature.
Originally published in Live Science.
