Scientists found that the SARS-CoV-2 backbone differed substantially from known coronaviruses and resembled related viruses found in bats and pangolins. Credit: Handout.

While US President Donald Trump has raised China’s ire by alleging the SARS-CoV-2 coronavirus may have escaped from a high-security lab in Wuhan, thereby shifting blame from his mishandling of the issue in the United States, a study published in the journal Nature Medicine, offers a purely scientific take.

The analysis of public genome sequence data from SARS-CoV-2 and related viruses came to the conclusion there was no evidence the virus was made in a lab or 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 Kristian Andersen, PhD, an associate professor of immunology and microbiology at Scripps Research and a corresponding author.

In addition to Andersen, the authors on the research paper, “The proximal origin of SARS-CoV-2,” reads like a who’s who of virus experts: Robert F. Garry, of Tulane University; Edward Holmes, of the University of Sydney; Andrew Rambaut, of University of Edinburgh; W. Ian Lipkin, of Columbia University — all top-ranking researchers in their fields.

While coronaviruses are a large family of viruses ranging widely in severity, the first known severe illness caused by a coronavirus emerged with the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic in China. A second outbreak of severe illness began in 2012 in Saudi Arabia with the Middle East Respiratory Syndrome (MERS).

On December 31 2019, Chinese authorities alerted the World Health Organization (WHO) of an outbreak of a novel strain of coronavirus, subsequently named SARS-CoV-2.

Shortly after the epidemic began, Chinese scientists sequenced the genome of SARS-CoV-2 and made the data available to researchers worldwide. Andersen and collaborators used this data to explore the mysterious origins and evolution of SARS-CoV-2.

The scientists 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, the report said.

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.

The scientists 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 report said.

The spike protein was so effective at binding human cells, in fact, that the scientists concluded it was the result of natural selection and not genetic engineering. This was also supported by data on SARS-CoV-2’s backbone – its overall molecular structure.

If someone were seeking to engineer a new 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 known coronaviruses and 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,” said Andersen, who concluded that the most likely origins followed one of two possible scenarios.

In one scenario, the virus evolved through natural selection in a non-human host and then jumped to humans. 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 involved.

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 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.

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.

Josie Golding, PhD, epidemics lead at UK-based Wellcome Trust, said the findings are “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.

“They conclude that the virus is the product of natural evolution,” Golding adds, “ending any speculation about deliberate genetic engineering.”

Scripps Research is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in La Jolla, Calif., with a sister facility in Jupiter, Fla., the institute has 250 laboratories employing 2,400 scientists, technicians, graduate students and administrative staff, making it the largest private, non-profit biomedical research organization in the US.