An analysis of the genomes of SARS-CoV-2, a novel coronavirus which causes COVID-19 disease, and related coronaviruses found no evidence that the virus was made in a laboratory or otherwise engineered.
Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image credit: NIAID.
Since the first reports of novel pneumonia COVID-19 in Wuhan, Hubei province, China, there has been considerable discussion on the origin of the causative virus, SARS-CoV-2.
Also known as 2019-nCoV, SARS-CoV-2 is the seventh coronavirus known to infect humans.
SARS-CoV-1, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms.
Shortly after the epidemic began, Chinese scientists sequenced the genome of SARS-CoV-2 and made the data available to researchers worldwide.
Dr. Kristian Andersen from the Department of Immunology and Microbiology at the Scripps Research Institute and colleagues used this sequencing data to explore the origins and evolution of SARS-CoV-2 by focusing in on several tell-tale features of the virus.
“By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 originated through natural processes,” Dr. Andersen said.
The researchers analyzed 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.
More specifically, they 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.
They found that 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 involved in regulating blood pressure.
The SARS-CoV-2 spike protein was so effective at binding the human cells, in fact, that the scientists concluded it was the result of natural selection and not the product of genetic engineering.
This evidence for natural evolution was supported by data on SARS-CoV-2’s molecular structure.
If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness.
But the scientists found that the SARS-CoV-2 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,” Dr. Andersen said.
Based on their genomic sequencing analysis, the team concluded that the most likely origins for SARS-CoV-2 followed one of two possible scenarios.
In one scenario, the virus evolved to its current pathogenic state through natural selection in a non-human host and then jumped to humans.
This is how previous coronavirus outbreaks have emerged, with humans contracting the virus after direct exposure to civets (SARS) and camels (MERS).
The researchers proposed bats as the most likely reservoir for SARS-CoV-2 as it is very similar to a bat coronavirus.
There are no documented cases of direct bat-human transmission, however, suggesting that an intermediate host was likely involved between bats and humans.
In this scenario, both of 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 — would have evolved to their current state prior to entering humans.
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.
In the other proposed scenario, a non-pathogenic version of the virus jumped from an animal host into humans and then evolved to its current pathogenic state within the human population.
For instance, some coronaviruses from pangolins, armadillo-like mammals found in Asia and Africa, have an RBD structure very similar to that of SARS-CoV-2.
A coronavirus from a pangolin could possibly have been transmitted to a human, either directly or through an intermediary host such as civets or ferrets.
Then the other distinct spike protein characteristic of SARS-CoV-2, the cleavage site, could have evolved within a human host, possibly via limited undetected circulation in the human population prior to the beginning of the epidemic.
The study authors found that the SARS-CoV-2 cleavage site, appears similar to the cleavage sites of strains of bird flu that has been shown to transmit easily between people.
SARS-CoV-2 could 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.
“It is difficult if not impossible to know at this point which of the scenarios is most likely,” said co-author Dr. Andrew Rambaut, a researcher in the Institute of Evolutionary Biology at the University of Edinburgh.
“If the SARS-CoV-2 entered humans in its current pathogenic form from an animal source, it raises the probability of future outbreaks, as the illness-causing strain of the virus could still be circulating in the animal population and might once again jump into humans.”
“The chances are lower of a non-pathogenic coronavirus entering the human population and then evolving properties similar to SARS-CoV-2.”
The study was published in the journal Nature Medicine.
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K.G. Andersen et al. The proximal origin of SARS-CoV-2. Nat Med, published March 17, 2020; doi: 10.1038/s41591-020-0820-9
