The authors of the article, which was published in the magazine PLOS Pathogensalso showed that this virus is resistant to antibodies in people vaccinated against SARS-CoV-2, which causes COVID-19, in laboratory tests.
The researchers said the study’s findings demonstrate that sarbecoviruses in wildlife outside Asia pose “a threat to global health” as well as to ongoing COVID-19 vaccination campaigns. Sarbecoviruses are a group of coronaviruses that includes SARS-CoV-2, SARS-CoV-1 (the cause of SARS, or severe acute respiratory syndrome), and several hundred genetically similar viruses found primarily in bats.
In the study, the researchers examined two sarbecoviruses, known as Khosta-1 and -2, which were discovered by Russian scientists in 2020 in the country’s southwestern Europe.
“Sarbecoviruses were originally thought, in the early 2000s, to only circulate in a specific type of local bat in southern China, but over the past 20 years scientists have discovered many more in diverse species and in different geographic locations,” Michael Letko, author. of the study at Washington State University, he said Newsweek.
So far, sarbecoviruses have been identified circulating in wildlife—such as bats, pangolins, raccoon dogs, and palm civets—in China, Laos, Japan, Russia, the United Kingdom, Africa, and Bulgaria.
It’s almost certain that researchers will discover more of these viruses in the future, Letko said.
Although hundreds of sarbecoviruses have been identified, many during efforts to determine the origins of SARS-CoV-1 and -2, most are not capable of infecting human cells. But several of these viruses have not yet been tested, so their ability to transmit to humans is unknown. Now, the authors of the new study have shown that Khosta-2, one of the newly discovered Russian sarbecoviruses, could use the same entry mechanisms to infect human cells that SARS-CoV-2 uses.
These findings have potential public health implications, given that a “spillover” of sarbecoviruses from animals to humans caused the original SARS outbreak and is believed to be the cause of the ongoing coronavirus pandemic. (A minority of experts have argued that, in the latter case, the virus may have originated from a laboratory leak.)
In the latest study, the researchers used a platform that Letko had previously developed to safely assess whether coronaviruses have the potential to infect humans. In January 2020, Letko used this platform to characterize the SARS-CoV-2 receptor.
The platform is fully in vitro, meaning experiments are performed in a laboratory outside of their normal biological context, in this case, using cell cultures and non-infectious viral particles.
“I would like to emphasize that there are no real viruses in our study, only molecular surrogates that cannot replicate and do not have any other coronavirus genes besides the spike protein,” which pathogens use to attach and enter the cells, Letko said.
“I’ve now started a lab expanding this research, so naturally when two new coronaviruses were discovered in Russia, I was very interested in testing them on my lab platform,” he said.
Among the key conclusions of the RAIN The study is that Russian Khosta viruses use the same receptor used by SARS-CoV-2, known as ACE2, to infect human cells.
“Although genetically related to SARS-CoV-2 only distantly, the Russian viruses are genetically more similar to other sarbecoviruses that have been found in Africa and elsewhere in Europe,” Letko said. “For the most part, the specific group of sarbecoviruses that the Khosta viruses belong to cannot bind to human ACE2 or infect human cells. Or so we thought.”
He continued: “The receptor used by any virus dictates which tissues the virus infects, which in turn relates to what types of disease symptoms the virus causes and how it is transmitted between hosts. Because Khosta-2 uses the same cell receptor human cells that SARS-CoV-2 and SARS-CoV-1, as well as some other seasonal coronaviruses, may be able to infect the same types of cells in humans.”
Second, the researchers found that blood serum from individuals vaccinated against COVID-19 did not neutralize the Khosta-2 virus under laboratory conditions, according to Letko. This was not necessarily surprising.
“One of the standard ways scientists measure the effectiveness of a vaccine is with a ‘neutralization assay,'” Letko said. “In this experiment, we combine viruses (or, in our case, virus-like particles ) with serum from people who have received the Moderna or Pfizer vaccines and then add to the cells in the test tubes. If the antibodies in the vaccinated person’s serum can bind to the virus, then the virus cannot infect the cells. We can measure that.
“When SARS-CoV-2 gets even a handful of new mutations, we call it a new variant, and it’s generally more resistant to vaccines. Because Khosta-2 is so different from SARS-CoV-2 , it’s not too surprising that the vaccines we use for SARS-CoV-2 can’t effectively prevent Khosta-2 from infecting cells,” Letko said.
Third, the team found that infection with the Omicron variant of the coronavirus may not protect against Khosta-2. Serum from people who had recovered from Omicron did not completely neutralize the virus. Again, because Khosta-2 is different enough, the vaccine is not effective.
Letko said it’s important to note that in the case of the second and third findings, it’s not possible to say with certainty that these responses actually mimic an infection in a real person, since the results come from cell culture experiments.
“It may be possible that the immune response in a real person is more diverse and effective than this simplified experimental system we use,” he said.
According to Letko, it is difficult to say at this stage whether Khosta-2 has the potential to cause an epidemic or even a pandemic.
“Just because the virus can infect human cells doesn’t mean it will cause a pandemic or even spread to a single person,” he said. “Many factors control whether a virus will be transmitted and whether it will spread between individuals with the high efficiency required for a pandemic.”
Letko continued, “At this time, we do not know the prevalence or likely true distribution of this virus in nature. As the original scientists who discovered the Khosta viruses noted in their study, [they] missing genes found in pathogenic human sarbecoviruses that are likely responsible for immune evasion and disease.”
What researchers are perhaps most concerned about is the potential for a process known as “recombination” to occur.
“We know pretty well from the last 40 years of coronavirus research that if two coronaviruses are genetically similar and in the same cell, they can recombine,” Letko said. “Bits in one genome can replace similar bits in the other genome, resulting in a hybrid genome of both viruses.”
Because SARS-CoV-2 and Khosta-2 are genetically similar enough to be called sarbecoviruses and can infect the same types of cells by the same mechanisms, it is possible that they recombine in a way that gives SARS-CoV -2. Khosta-2 vaccine resistance while retaining other virulence characteristics of SARS-CoV-2.
“The chances of SARS-CoV-2 ever encountering Khosta-2 in nature is very small, but there have been an increasing number of reports describing SARS-CoV-2 re-shedding in the wildlife, like white-tailed deer on the East Coast of the United States,” Letko said. “This is all a worst-case scenario, but it’s just one of the things we think about in my lab as we try to prevent the next pandemic from happening again.”