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Potenziell infektiöses Coronavirus in russischen Fledermäusen – Coronavirus kann an humanem ACE2-Rezeptor andocken, macht aber (noch) nicht krank

Potential danger? Cell culture tests show that the coronavirus found in Russian bats can infect human cells. In them, this virus, known as Hosta-2, docked with the human ACE2 receptor and infected the cells. This bat coronavirus is still missing some of the disease-causing gene segments, so infection is likely to have little impact. But if this animal virus comes into contact with and recombines with SARS-CoV-2, a new pathogen resistant to our vaccines could emerge, the researchers warn.

At least after SARS, MERS and the current corona pandemic, it has become clear that corona viruses, which are widespread in animals, can also spread to humans. Their high adaptability makes animal coronaviruses a reservoir for future pathogens. Several coronaviruses have already been found in Asian bats that are very similar to SARS-CoV-2 and whose spike protein can dock with ACE2 receptors on human cells. Some researchers even suspect that there are persistent undetected cases of infection with such animal coronaviruses in Southeast Asia.

spike protein
Spike protein of SARS-CoV-2 coronavirus. Its configuration determines how well a variant of the virus can attach to human cells. © NIAID

New coronaviruses in Russian bats

But potentially infectious animal coronaviruses are not limited to Southeast Asia, as Stephanie Seifert of the University of Washington and her colleagues recently discovered. For their study, they took a closer look at the characteristics and behavior of two coronaviruses found in Russia. These viruses, named Hosta-1 and Hosta-2, were found in two species of horseshoe bats at the end of 2020. Like SARS-CoV-2, they belong to the sarbecovirus subgenus.

“Because these Russian coronoviruses looked different than SARS-CoV-2, at first no one thought they were particularly interesting,” explains Seifert’s colleague Michael Letko. The surface proteins of host coronaviruses differ significantly from the pandemic pathogen in some sugar deposits and molecular loops, which is why they were not considered as a potential hazard to humans. To test this, the team created pseudoviruses with a hostavirus receptor binding site located on a spike protein and tested whether they could infect two human cell lines.

Hosta-2 can infect human cells

Result: Hosta-1 was found to be harmless to human cells, but not Hosta-2. “We were very surprised that this virus could infect human cells,” Letko says. During the tests, the binding site of the Russian animal virus was able to dock with the ACE2 receptor on human cells and thus enter them. Thus, the Host-2 virus used the same portal of entry as SARS-CoV-2, although the infectivity was lower compared to the Covid-19 pathogen, the team reports.

A more detailed analysis showed that the Host-2 virus differs significantly from SARS-CoV-2 in many other protein structures, but not in the binding site. “About 60 percent of its configuration matches various variants of SARS-CoV-2,” Seifert and her colleagues report. Thus, the key structures of the spike protein are similar enough that it can be attached to human cells. “This suggests that sarbecoviruses circulating in animals outside of Asia may also pose a potential threat to human health,” Letko says.

Recombination can make a virus pathogenic

However, the Host-2 coronavirus would not yet be dangerous even if it infected people. Because several gene segments are missing that contribute to the pathogenic action of SARS-CoV-2. As a result, the human immune system quickly recognizes these viruses and neutralizes them before symptoms of the disease develop, the scientists explain.

“Unfortunately, coronaviruses are also known to be able to recombine in coinfected hosts,” Seifert and her team explain. This means that if an animal or person is infected with two different coronaviruses at the same time, these pathogens can exchange genes with each other and thus form new types of hybrid viruses. If Hosta-2 virus encounters SARS-CoV-2 in such a double-infected host, a new disease-causing mixed virus could emerge.

With transmission of SARS-CoV-2 back to wild animals already proven, this recombination is a very realistic scenario, the team emphasizes. “There are also wild animals and a number of other coronaviruses whose properties we definitely don’t need in Host-2,” Letko says. Ultimately, therefore, the emergence of new human pathogenic variants of the coronavirus is only a matter of time.

Broad Spectrum Vaccines Needed

According to Seifert and her team, it is all the more important to develop widely effective vaccines and treatments. They should be effective not only against SARS-CoV-2, but also against yet-to-be-discovered corona viruses. Because, as the researchers determined in their tests, current antibody therapies and vaccines cannot neutralize the Host-2 coronavirus. Even previous exposure to Covid-19 will not protect against infection.

“There are already several research groups working on such a broad-spectrum vaccine against sarbecoviruses,” Letko says. A recently presented prototype of such a broad-spectrum vaccine uses special nanoparticles that carry the protein regions of eight different coronaviruses on their surface. As a result, the immune system produces more antibodies against the common protein regions of the corona virus and is thus able to fight off variants of the virus not contained in the vaccine. (PLoS Pathogens, 2022; doi:10.1371/journal.ppat.1010828)

Quelle: PLOS, University of Washington.

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