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COVID-19 coronavirus epidemic has a natural origin

Coronaviruses are a big family of viruses which can cause illnesses ranging widely in severity. The very first known acute illness caused by a coronavirus appeared together with the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak in China.

On December 31 of the last year, Chinese police alerted the World Health Organization of an epidemic of a novel strain of coronavirus causing severe disease, which was then named SARS-CoV-2. As of February 20, 2020, nearly 167,500 COVID-19 cases are documented, although many more mild cases have likely gone undiagnosed. The virus has killed over 6,600 people.

Shortly after the epidemic began, Chinese scientists sequenced the genome of both SARS-CoV-2 and created the data available to researchers worldwide. The consequent genomic sequence data has demonstrated that Chinese governments rapidly discovered that the outbreak and that the amount of COVID-19 cases have been increasing because of human to human transmission after a single introduction to the human inhabitants. Andersen and collaborators at several other research institutions used this sequencing information to explore the origins and evolution of SARS-CoV-2 by focusing on many tell-tale characteristics of the virus.

The scientists analyzed the genetic template for spike proteins, armatures on the outside of the virus that it uses to grab and permeate the outer walls of both human and animal cells.

Evidence for natural development

The scientists found the RBD portion of those SARS-CoV-2 spike proteins had evolved to effectively target a molecular characteristic on the outside of human cells called ACE2, a receptor involved in regulating blood pressure. The SARS-CoV-2 spike protein was really effective at binding the human cells, in reality, the scientists reasoned it had been the result of natural selection and not the product of genetic engineering.

This proof for natural development has been supported by info on SARS-CoV-2's backbone -- its overall molecular structure. If a person were seeking to engineer a new coronavirus as a pathogen, then they'd have constructed it from the backbone of a virus known to cause sickness. However, the scientists discovered that the SARS-CoV-2 backbone differed greatly from those of already known coronaviruses and mostly resembled related viruses discovered in rodents and pangolins.

"These two features of this virus, the mutations from the RBD part of the spike protein and its own distinct backbone, rules out lab manipulation as a possible source for SARS-CoV-2" explained Andersen.

Josie Golding, PhD, epidemics lead at UK-based Wellcome Trust, said the findings from Andersen and his colleagues have been"crucially important to bring an evidence-based opinion into the rumors which 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 development," Goulding adds,"finish any speculation about willful genetic engineering"

Possible origins of this virus

In one situation, the virus evolved into its present pathogenic condition through natural selection in a non invasive host and then jumped into people. This is the way previous coronavirus outbreaks have emerged, together with humans contracting the virus after direct exposure to civets (SARS) and camels (MERS). The researchers proposed bats since the most likely reservoir for SARS-CoV-2 since it's extremely like a bat coronavirus. There are no documented instances of direct bat-human transmission, however, suggesting that an intermediate host was probably involved between individuals and people.

In this scenario, both of the distinctive attributes of SARS-CoV-2's spike protein -- the RBD part that binds to cells along with the cleavage site that opens the virus up -- could have evolved into their current state prior to entering people. In this case, the current epidemic would most likely have emerged rapidly when people were infected, since the virus could have already evolved the features that make it pathogenic and ready to spread between people.

In another suggested scenario, a non-pathogenic variant of the virus jumped from an animal host to humans and then evolved to its present pathogenic state inside the human inhabitants. For example, some coronaviruses out of pangolins, armadillo-like mammals found in Asia and Africa, have an RBD structure very similar to that of SARS-CoV-2. A coronavirus out of a pangolin could possibly have been transmitted to a person, either directly or through an intermediary host such as civets or ferrets.

Then another distinct spike protein characteristic of SARS-CoV-2, the cleavage site, might have evolved inside an individual host, maybe via restricted undetected circulation in the human population prior to the beginning of the outbreak. The researchers found that the SARS-CoV-2 cleavage site, appears similar to the cleavage sites of breeds of bird flu that's been shown to transmit easily between humans. SARS-CoV-2 might have developed such a virulent cleavage site in human cells and kicked off the present epidemic, since the coronavirus would possibly have become a lot more capable of spreading between people.

Study co-author Andrew Rambaut cautioned it is difficult if not impossible to know at this stage which of the scenarios is probably. If the SARS-CoV-2 entered people in its current pathogenic form from an animal source, it increases the probability of future outbreaks, as the illness-causing strain of the virus may still be circulating in the animal population and might once again jump into humans. The chances are reduced of a non-pathogenic coronavirus entering the human inhabitants and then evolving properties much like SARS-CoV-2.

Funding for the study was provided by the US National Institutes of Health, the Pew Charitable Trusts, the Wellcome Trust, the European Research Council, and an ARC Australian Laureate Fellowship.

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