Coronavirus Evolved Naturally & ‘Not A Lab Construct’, Genetic Study Shows

Transmission electron microscope image of an isolate of the first U.S. case of COVID-19, formerly known as 2019-nCoV. The spherical viral particles, stained blue, contain cross sections through the viral genome, seen as black dots. [CDC/ Hannah A Bullock; Azaibi Tamin]

Researchers at the Scripps Research Institute say their genetic analysis of the SARS-CoV-2 coronavirus and related viruses has found no evidence that SARS-CoV-2 is the result of bioengineering in a laboratory. On the contrary, said Kristian Andersen, PhD, associate professor of immunology and microbiology at Scripps Research and corresponding author of the report published in Natural medicine, “By comparing the genome sequence data available for known coronavirus strains, we can determine with certainty that SARS-CoV-2 arose from natural processes. And as Andersen and his colleagues concluded, the results “clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully engineered virus.”

Andersen is the corresponding author of the team article, titled “The Proximal Origin of SARS-CoV-2”. Co-authors include Robert F. Garry, PhD, professor at Tulane University; Edward Holmes, PhD, professor at the University of Sydney; Andrew Rambaut, PhD, professor at the University of Edinburgh; and W. Ian Lipkin, PhD, professor at Columbia University.

Coronaviruses are a large family of viruses that can cause illnesses that vary in severity. The first known serious illness caused by coronavirus emerged with the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic in China. A second epidemic of serious illness began in 2012 in Saudi Arabia with Middle East Respiratory Syndrome (MERS). In fact, “SARS-CoV-2 is the seventh coronavirus known to infect humans,” the authors wrote. But unlike MERS-CoV and SARS-CoV, which can cause serious illness, “… HKU1, NL63, OC43 and 229E are associated with mild symptoms. “

On December 31 last year, Chinese authorities alerted the World Health Organization to an outbreak of a new strain of coronavirus causing severe illness, which was later named SARS-CoV-2. As of March 17, there have been 179,111 confirmed cases and 7,426 coronavirus-related deaths, according to WHO figures.

Shortly after the outbreak began, Chinese scientists sequenced the SARS-CoV-2 genome and made the data available to researchers around the world. The resulting genomic sequence data showed that Chinese authorities quickly detected the outbreak and that the number of COVID-19 cases increased due to human-to-human transmission after a single introduction into the human population.

Andersen and colleagues used this sequencing data to explore the origins and evolution of SARS-CoV-2 by focusing on the telltale characteristics of the virus. “We review what can be inferred about the origin of SARS-CoV-2 from the comparative analysis of genomic data,” they wrote. “We offer a perspective on notable features of the SARS-CoV-2 genome and discuss scenarios under which they could have arisen. “

For their studies, the scientists analyzed the genetic model of viral spike proteins outside of SARS-CoV-2 that the virus uses to bind to cell surface receptors and enter human host cells. They focused on two important characteristics of the spike protein: the receptor binding domain (RBD) and the polybasic furin cleavage site of the spike, which is involved in entry through the outer membrane of the spike. host cell, makes it a molecular can opener.

This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals the ultrastructural morphology exhibited by coronaviruses. A new coronavirus, named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of respiratory disease first detected in Wuhan, China, in 2019. The disease caused by this virus was named coronavirus disease 2019 (COVID-19). [CDC/Alissa Eckert, MS]

Scientists found that the RBD portion of SARS-CoV-2 spike proteins evolved to effectively target the host cell’s ACE2 receptor, which is involved in regulating blood pressure, with high affinity. However, they pointed out, the RBD of SARS-CoV-2 is optimized to bind to human ACE2 with an effective solution different from those previously predicted. “Thus, the high affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 which allows another solution to optimal binding to appear, ”they said. This, they noted, represented “strong evidence that SARS-CoV-2 is not the product of deliberate manipulation.”

The evidence for the virus’s natural history was supported by data on the SARS-CoV-2 backbone, its overall molecular structure. If someone were looking to design a new coronavirus as a pathogen, they would have built it from the backbone of a virus known to cause disease. But scientists found that the SARS-CoV-2 skeleton differed significantly from those of already known coronaviruses, and mostly resembled related viruses found in bats and pangolins. “… the genetic data shows conclusively that SARS-CoV-2 is not derived from any previously used viral backbone,” the scientists said in their report. Andersen added: “These two characteristics of the virus, mutations in the RBD part of the spike protein and its distinct backbone, preclude laboratory manipulation as a potential origin of SARS-CoV-2. “

Based on their genomic sequencing analysis, Andersen and colleagues concluded that the course of SARS-CoV-2 followed one of two possible scenarios from its origins. In one scenario, the virus evolved to its current pathogenic state by natural selection in a non-human host and then jumped onto humans. This is how previous coronavirus outbreaks have emerged, with humans contracting the virus after direct exposure to civets, in the case of SARS, and to camels, in the case of MERS. The researchers proposed bats as the most likely reservoir of SARS-CoV-2 because this virus is very similar to a bat coronavirus. There are, however, no documented cases of direct bat-to-human transmission, suggesting that an intermediate host was likely involved somewhere between bats and humans.

In this first scenario, the two distinctive features of the SARS-CoV-2 spike protein – the RBD part that binds to cells and the cleavage site involved in introducing the virus into the host cell – would have evolved into their current conditions before the virus jumping to humans. The spread of SARS-CoV-2 would then likely have been rapid, once humans were infected, as the virus would have already developed the key characteristics that make it pathogenic and capable of transmission between people. “

In the other proposed scenario, a non-pathogenic version of the virus has passed from an animal host to humans and then evolved to its current pathogenic state in the human population. For example, some pangolin coronaviruses 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 intermediate host, such as civets or ferrets. In this scenario, the other distinct spike protein characteristic of SARS-CoV-2, the cleavage site, could have evolved within a human host, possibly via limited circulation not detected in the human population before the onset of the epidemic.

“The presence in the pangolins of an RBD very similar to that of SARS-CoV-2 means that we can infer that it was probably also in the virus that jumped to humans,” noted the authors. “This allows the insertion of the polybasic cleavage site to occur during human-to-human transmission.” Indeed, there would be a period of “unrecognized transmission” in humans, between the initial jump from animal to human, or the zoonotic event, and the acquisition of the polybasic cleavage site.

The researchers also found that the cleavage site of SARS-CoV-2 appears similar to the cleavage sites of strains of avian flu that are easily transmitted between people. It is possible that SARS-CoV-2 developed such a virulent cleavage site in human cells, in which case the coronavirus might have become much more capable of spreading between people, and this is how the epidemic has started.

Study co-author Rambaut warned that it is difficult, if not impossible, to know at this point which of the scenarios is the one that actually unfolded. “More scientific data could tip the balance of evidence in favor of one hypothesis or another,” the researchers acknowledged.

If SARS-CoV-2 entered humans in its current pathogenic form from an animal source, this would increase the likelihood of future outbreaks, as the pathogenic strain of the virus could still circulate in the animal population and could again spread in humans. The chances are lower that a non-pathogenic coronavirus will enter the human population and then develop properties similar to SARS-CoV-2. Regardless of the most likely scenario, the researchers reiterated that “… since we observed all notable features of SARS-CoV-2, including the optimized RBD and polybasic cleavage site, compared to coronaviruses in the nature, we don’t think any kind of lab scenario is plausible.

Josie Golding, PhD, epidemic manager at UK-based Wellcome Trust, who is not one of the authors of the article, said the findings of Andersen and his colleagues are “fundamentally 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 ”. Goulding noted: “They conclude that the virus is the product of natural evolution, ending all speculation about deliberate genetic engineering.”

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