The novel coronavirus that has caused the COVID-19 pandemic is not artificially made, but the product of natural evolution, a new study says, ending widespread speculation and rumours that the virus may have been engineered in a lab.
In the study, published in the journal Nature Medicine, researchers analysed the publicly available genome sequence data of the novel coronavirus, SARS-CoV-2, and related viruses.
The scientists, including those from The Scripps Research Institute in the US, said they did not find any evidence that the virus was made in a laboratory or otherwise engineered.
"By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 originated through natural processes," said study co-author Kristian Andersen from The Scripps Research Institute.
They said the sequence data has shown that Chinese authorities rapidly detected the epidemic, and that the number of COVID-19 cases have been increasing because of human to human transmission after a single introduction into the human population.
Using this sequence data, the researchers traced the origins and evolution of SARS-CoV-2 by focusing on the tell-tale features of the virus.
To do this, the scientists said they analysed the genetic template for spike proteins -- armatures on the outside of the virus that it uses to grab and penetrate the outer walls of human and animal cells.
The study focused on two important features of the spike protein -- the receptor-binding domain (RBD), a kind of grappling hook that grips onto host cells, and the cleavage site, a molecular can opener that allows the virus to crack open and enter host cells.
According to the study, the RBD portion of the SARS-CoV-2 spike proteins had evolved to effectively target a molecular feature on the outside of human cells called ACE2 -- a receptor protein involved in regulating blood pressure.
The spike protein of the novel coronavirus was so effective at binding the human cells that the researchers said it was the result of natural selection and not the product of genetic engineering.
They said this was supported by data on SARS-CoV-2's overall molecular structure.
If the new coronavirus were engineered as a pathogen, the scientists said, it must have been constructed from the backbone of a virus already known to cause illness.
But the study found that SARS-CoV-2's backbone differed substantially from those of already known coronaviruses, and mostly resembled related viruses found in bats and pangolins.
"These two features of the virus, the mutations in the RBD portion of the spike protein and its distinct backbone, rules out laboratory manipulation as a potential origin for SARS-CoV-2," Andersen said.
The researchers said the findings are crucially important to bring an evidence-based view to the rumours that have been circulating about the origins of SARS-CoV-2.
Based on their genomic sequencing analysis, Andersen and his team concluded that the most likely origins for SARS-CoV-2 followed one of two possible scenarios.
In one scenario, they said, the virus may have evolved to its current pathogenic state through natural selection in a non-human host and then jumped to humans.
The researchers said previous coronavirus outbreaks emerged in a similar way, with humans contracting the virus after direct exposure to civets (SARS), and camels (MERS).
They proposed that bats are the most likely reservoir for SARS-CoV-2 as the virus is very similar to a bat coronavirus.
However, they said there are no documented cases of direct bat-human transmission, suggesting that an intermediate host was likely involved between bats and humans.
In this scenario, they said both the distinctive features of SARS-CoV-2's spike protein -- the RBD portion that binds to cells, and the cleavage site that opens the virus up -- may have evolved to their current state prior to entering humans.
The scientists noted that in this case, the current epidemic would probably have emerged rapidly as soon as humans were infected, as the virus would have already evolved the features that make it pathogenic, and able to spread between people.
They added that a non-pathogenic version of the virus may have jumped from an animal host into humans, and then evolved to its current disease-causing state within the human population.
Citing an example, the researchers said, some coronaviruses from pangolins -- armadillo-like mammals found in Asia and Africa -- have an RBD structure very similar to that of SARS-CoV-2.
They said a coronavirus from a pangolin may have been transmitted to a human, either directly, or through an intermediary host such as civets or ferrets.
The distinct spike protein characteristic of SARS-CoV-2, the cleavage site, may have then evolved within a human host, possibly through limited undetected circulation in the human population prior to the beginning of the epidemic, the study said.
The scientists also found that the SARS-CoV-2 cleavage site appeared similar to the cleavage sites of strains of bird flu that had been shown to transmit easily between people.
They speculated that SARS-CoV-2 may have evolved such a virulent cleavage site in human cells, and soon kicked off the current epidemic, as the coronavirus would possibly have become far more capable of spreading between people.
However, the scientists cautioned that it is difficult, if not impossible, to know at this point which of the scenarios is most likely.
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