Origin of the coronavirus: closest Sars

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Bats in a cave

Photo: remus20 / imago images / remus20

In caves in Laos, experts have discovered three coronaviruses in bats that are more similar to Sars-CoV-2, the pathogen that triggered the current pandemic, than any other known virus.

It is particularly noteworthy that the binding domains of the newly detected pathogens are almost identical to those of the pandemic virus, the particles can also infect human cells.

Experts take this as a further indication that Sars-CoV-2 developed naturally.

The origin of the virus that causes the Covid-19 disease has not yet been found. There are many indications that the pathogen has passed from a bat - or via another wild animal as an intermediate host - to humans. Another thesis says that Sars-CoV-2 could come from a laboratory. So far, both theses can neither be clearly refuted nor clearly proven.

For the current study, international experts led by the virologist Marc Eloit from the renowned Pasteur Institute in Paris collected saliva, feces and urine samples from 645 bats in limestone caves in the north of Laos.

In three species of horseshoe bat (Rhinolophus), which have long been known as large reservoirs for coronaviruses, they found viruses whose genome is more than 95 percent identical to that of Sars-CoV-2.

The study was published in advance on the “Research Square” platform and is to appear in a “Nature” specialist journal, but an examination by independent experts is still missing.

Big similarities at the receptor binding site

The three detected pathogens are named Banal-52, Banal-103 and Banal-236. According to the analysis, Banal-52 has the greatest similarity with the cause of the current pandemic, with a genetic match of 96.8 percent. The previously closest known relative of Sars-CoV-2 with a 96.1 percent identical genome bears the name RaTG13 and was detected in 2013 in horseshoe-nosed bats in the province of Yunnan in southern China.

However, it is not only the extent of the genetic match that is decisive, but also in which areas the viruses are similar. The current analysis showed particularly great similarities at central locations: The receptor binding sites with which all three newly discovered viruses penetrate host cells are therefore more similar to those of Sars-CoV-2 than any other known virus. As the first known close relatives of the Covid-19 pathogen, the particles are able to bind to human cells.

The binding domain of Sars-CoV-2 is on the spike protein of the virus. With it, the pathogen can dock on so-called ACE2 receptors on human cells and infect them. According to the study, the binding domains of the newly discovered viruses have a similar affinity for the ACE2 receptor as that of the Sars-CoV-2 lines that circulated at the beginning of the pandemic. In animal models, Eloit and his team now want to check whether the pathogens are also as pathogenic as Sars-CoV-2.

"When Sars-CoV-2 was first sequenced, the receptor binding domain didn't really look like something we had seen before," said Edward Holmes, a virologist at the University of Sydney in Australia who was not involved in the current work , the specialist magazine "Nature".

This has led some people to believe that the virus may have been created in a laboratory.

However, the corona viruses from Laos have now confirmed that the initially unknown virus structures occur in nature.

Furin binding site puzzle

It remains unclear, however, where Sars-CoV-2 got its so-called furin cleavage site in the spike protein. Furin cleavage sites significantly increase the ability of viruses to enter human cells. Various coronaviruses contain such elements, but Sars-CoV-2 is the only known Sarbecovirus, a subgenus of the beta coronaviruses that has a furin cleavage site. This can be interpreted as an indication that the virus could have been generated in the laboratory.

A few days ago it became known that the New York NGO EcoHealth Alliance (EHA) had submitted a funding application to DARPA, the research division of the US Department of Defense, for a project in which experts wanted to insert furin cleavage sites into Sars-like viruses. However, the request was denied. In addition, the Sars-CoV-2 cleavage site does not work particularly efficiently, which in turn speaks against the fact that it was specifically integrated. (Read more about it here).

The thesis that Sars-CoV-2 has passed from an animal to a human is supported by the fact that this is the case with an estimated six out of ten of all known human infectious diseases. In the recent past three out of four new infectious diseases in humans were of animal origin. Such so-called zoonoses include HIV, rabies, plague, Zika, malaria and Ebola. The first known Sars virus, which caused an epidemic with almost 800 deaths at the beginning of the noughties, also came with great certainty from an animal.

Southeast Asia has long been a haven for countless corona viruses. Since game meat is sold in markets here and then consumed, people there come into contact with the pathogens again and again. "The danger of a zoonotic spillovers is known to be very high," said zoologist Matthias Glaubrecht from the University of Hamburg recently to SPIEGEL. "And the south of China is particularly at risk."

Many experts consider it plausible that even before the Sars-CoV-2 outbreak in Wuhan, which is considered the beginning of the corona pandemic, precursors of the virus were circulating in southern China or neighboring states such as Laos, but they were not there could spread efficiently.

The 11 million metropolis of Wuhan could ultimately have taken on a distribution function.

However, the exact pathways of the virus and its exact origin remain unclear.