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SARS-CoV-2 not Man-Made, Comparative Genomic Study Concludes

NEW YORK – The SARS-CoV-2 virus behind the ongoing COVID-19 pandemic evolved from naturally occurring strains, according to a new comparative genomic analysis.

"By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 originated through natural processes," corresponding author Kristian Andersen, an immunology and microbiology researcher affiliated with the Scripps Research Institute and the Scripps Research Translational Institute, said in a statement. 

As they reported in a correspondence article published in Nature Medicine on Tuesday, Andersen and colleagues from the US, Australia, and the UK brought together publicly available genome sequence data for alpha- and beta-coronaviruses found in a wide range of animal hosts, along with data from SARS-CoV-2 isolates and other coronaviruses infecting humans.

The team saw signs of natural selection acting on key coronavirus genome features such as the receptor-binding domain (RBD) sequences and sequences spanning so-called "polybasic cleavage sites," which contribute to spike protein characteristics that help the virus latch on to, and blast into, animal cells.

"The genomic features described here may explain in part the infectiousness and transmissibility of SARS-CoV-2 in humans," the authors wrote, adding that "since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible."

When it came to the spike protein RBD, for example, the researchers discovered that the version found in SARS-CoV-2 appears to be particularly adept at interacting with human cell surface proteins, such as the blood pressure-related receptor ACE2.

Likewise, the investigators noted that the SARS-CoV-2 backbone sequence was not altered in a way that might be expected by genetic engineering, but instead lined up with coronaviruses that have been documented in animal hosts such as bats or pangolins.

"Malayan pangolins (Manis javanica) illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-2," the authors noted. "Although the RaTG13 bat virus remains the closest to SARS-Cov-2 across the genome, some pangolin coronaviruses exhibit strong similarity to SARS-CoV-2 in the RBD, including all six key RBD residues."

The virus behind COVID-19 is the seventh coronavirus found so far that is capable of infecting humans, the researchers explained, noting that four of them produce much milder symptoms. The remaining three coronaviruses — including the virus behind the 2003 SARS outbreak, the Middle East Respiratory Syndrome culprit MERS-CoV, and SARS-CoV-2 — can lead to much more severe conditions.

In the months since the SARS-CoV-2 coronavirus turned up in Wuhan, China, speculations have popped up around its origins, with some wondering whether the strain stemmed from a lab escape or alternative non-natural source.

The researchers' analyses argue against that possibility, pointing instead to human infections stemming from either pathogenic SARS-CoV-2 viruses that were transmitted from an animal vector to humans or from initially non-pathogenic forms of the virus that evolved in humans to become pathogenic — possibilities that will be explored further in the future.

"They conclude that the virus is the product of natural evolution, ending any speculation about deliberate genetic engineering," Josie Golding, an epidemic preparedness and response program officer at the Wellcome Trust, who was not involved in the study, said in a statement, calling the results "crucially important to bring an evidence-based view to the rumors that have been circulating about the origins of the virus (SARS-CoV-2) causing COVID-19."