The novel SARS-CoV-2 coronavirus
that emerged in the city of Wuhan, China, last year and has since caused a
large scale COVID-19 epidemic and spread to more than 70 other countries is the
product of natural evolution, according to findings published in the journal Nature
Medicine.
The analysis of
public genome sequence data from SARS-CoV-2 and related viruses found no
evidence that the virus was made in a laboratory or otherwise 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 corresponding author on the paper.
In addition to
Andersen, authors on the paper, “The proximal origin of SARS-CoV-2,” include
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.
Coronaviruses
are a large family of viruses that can cause illnesses 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
of last year, Chinese authorities alerted the World Health Organization of an
outbreak of a novel strain of coronavirus causing severe illness, which was
subsequently named SARS-CoV-2. As of February 20, 2020, nearly 167,500 COVID-19
cases have been 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 SARS-CoV-2 and
made the data available to researchers worldwide. The resulting genomic
sequence data has shown that Chinese authorities rapidly detected the epidemic
and that the number of COVID-19 cases have been increasing because of human to
human transmission after a single introduction into the human population.
Andersen and collaborators at several other research institutions 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.
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. 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.
Evidence for natural evolution
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 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 backbone — its
overall 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” said Andersen.
Josie Golding,
PhD, epidemics lead at UK-based Wellcome Trust, said the findings by Andersen
and his colleagues 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,” Goulding adds, “ending any
speculation about deliberate genetic engineering.”
Possible origins of the virus
Based on their
genomic sequencing analysis, Andersen and his collaborators 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 researchers
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.
Study co-author
Andrew Rambaut cautioned that it is difficult if not impossible to know at this
point which of the scenarios is most likely. 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.
Source: https://www.scripps.edu/news-and-events/press-room/2020/20200317-andersen-covid-19-coronavirus.html
Journal article: https://www.nature.com/articles/s41591-020-0820-9
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