Potential danger? A coronavirus discovered in Russian bats can infect human cells, cell culture tests reveal. In them, this virus, known as Khosta-2, docked onto the human ACE2 receptor and infected the cells. This bat coronavirus is still missing some disease-causing gene segments, so an infection would probably have few consequences. But if this animal virus comes into contact with and recombines with SARS-CoV-2, a new pathogen that is resistant to our vaccines might arise, researchers warn.
At least since SARS, MERS and the current corona pandemic, it has been clear that corona viruses that are widespread in animals can also spread to humans. Their high adaptability makes the animal corona viruses a reservoir for future pathogens. In Asian bats have been multiple coronaviruses proven the SARS-CoV-2 very similar and whose spike protein can dock to the ACE2 receptors on human cells. Some researchers even suspect that it is constantly in Southeast Asia recognized infections with such animal coronaviruses.
New coronaviruses in Russian bats
But potentially infectious animal coronaviruses are not only found in Southeast Asia, as Stephanie Seifert from Washington State University and her colleagues have now discovered. For their study, they examined the characteristics and behavior of two corona viruses discovered in Russia in more detail. These viruses, dubbed Khosta-1 and Khosta-2, were discovered in two species of horseshoe bats in late 2020. Like SARS-CoV-2, they belong to the sarbecovirus subgenus.
“Because these Russian corona viruses looked different from SARS-CoV-2, nobody initially thought they were particularly exciting,” explains Seifert’s colleague Michael Letko. The surface proteins of the Khosta coronaviruses differ significantly from the pandemic pathogen in some sugar deposits and molecular loops – which is why they were not seen as a potential danger to humans. To test this, the team created pseudoviruses with the Khostavirus receptor binding site located on the spike protein and tested whether they might infect two human cell lines.
Khosta-2 can infect human cells
The result: Khosta-1 proved to be harmless for human cells, but not Khosta-2. “We were really surprised that this virus can infect human cells,” says Letko. In the test, the binding site of the Russian animal virus was able to dock onto the ACE2 receptor of human cells and thus penetrate them. The Khosta-2 virus thus used the same portal of entry as SARS-CoV-2, although the infectivity was lower than that of the Covid-19 pathogen, as the team reports.
More detailed analyzes revealed that the Khosta-2 virus differs significantly from SARS-CoV-2 in many other protein structures, but not in its binding site. “This shares around 60 percent of its configuration with different variants of SARS-CoV-2,” report Seifert and her colleagues. The crucial structures of the spike protein are therefore similar enough to be able to dock onto human cells. “This demonstrates that sarbecoviruses that circulate in animals outside of Asia can also pose a potential threat to human health,” says Letko.
Recombination might make the virus pathogenic
However, the Khosta-2 corona virus would not yet be dangerous even if it were to infect humans. Because it is missing several gene segments that contribute to the pathogenic effect of SARS-CoV-2. As a result, the human immune system would quickly recognize these viruses and render them harmless before symptoms of the disease develop, as the scientists explain.
“Unfortunately, coronaviruses are also known to be able to recombine in co-infected hosts,” explains Seifert and her team. This means: If an animal or human is infected with two different corona viruses at the same time, these pathogens can exchange genes with each other and thus form new hybrid virus types. If the Khosta-2 virus now encounters SARS-CoV-2 in such a doubly infected host, a novel, disease-causing mixed virus might arise.
In view of the fact that transmissions of SARS-CoV-2 back to wild animals have already been proven, such a recombination is a very realistic scenario, the team emphasizes. “There are also wild animals and a whole range of other corona viruses whose properties we definitely do not want in Khosta-2,” says Letko. Ultimately, it is therefore only a matter of time before new human-pathogenic coronavirus variants appear.
Broad-spectrum vaccines needed
In the opinion of Seifert and her team, it is therefore all the more important to develop broadly effective vaccines and therapies. These would not only have to be effective once morest SARS-CoV-2, but also once morest as yet undiscovered corona viruses. Because, as the researchers determined in their tests, the current antibody therapies and vaccines cannot neutralize the Khosta-2 coronavirus. Even a previous infection with Covid-19 would not protect once morest infection.
“There are already several research groups working on such a vaccine that has a broad effect once morest sarbecoviruses,” says Letko. A recently introduced one Prototype for such a broad-spectrum vaccine uses special nanoparticles that carry protein sections from eight different corona viruses on their surface. As a result, the immune system produces more antibodies once morest the common protein sections of the corona virus – and can thus fend off virus variants that are not contained in the vaccine. (PLoS Pathogens, 2022; doi: 10.1371/journal.ppat.1010828)
Quelle: PLOS, Washington State University
