A SARS-CoV-2 virus relative that was originally found in Russian bats may be capable of infecting human cells, according to a study.
The authors of the paper, which was published in the journal PLOS Pathogens, also showed that this virus is resistant to the antibodies of people vaccinated against SARS-CoV-2—which causes COVID-19—in lab tests.
The researchers said the study’s findings demonstrate that sarbecoviruses in wildlife outside of 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 mostly in bats.
In the study, the researchers examined two sarbecoviruses—known as Khosta-1 and -2—that were discovered by Russian scientists in 2020 in the country’s European southwest.
“Sarbecoviruses were originally thought—in the early 2000s—to only circulate in a specific type of bat local to southern China, but over the past 20 years scientists have discovered many more in diverse species and different geographic locations,” Michael Letko, an author of the study who is with Washington State University, told Newsweek.
To date, sarbecoviruses have been identified as circulating in wildlife—such as bats, pangolins, raccoon dogs and palm civets—in China, Laos, Japan, Russia, the United Kingdom, Africa and Bulgaria.
It is almost certain that researchers will uncover more of these viruses in the future, Letko said.
While 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 remain untested, and therefore 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 resulted in the original SARS outbreak and is thought to have been 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 lab leak.)
In the latest study, the researchers used a platform that Letko had previously developed to safely assess if coronaviruses have the potential to infect humans. In January 2020, Letko used this platform to characterize the receptor for SARS-CoV-2.
The platform is entirely in vitro, meaning experiments are conducted in a lab outside their normal biological context—in this case, using cell cultures and noninfectious viral-like particles.
“I would like to emphasize there is no actual virus in our study—only molecular surrogates that cannot replicate and do not have any other coronavirus genes besides the spike protein,” which the pathogens use to bind to and enter cells, Letko said.
“I have now started a laboratory expanding on this research, so naturally when two new coronaviruses were discovered in Russia, I was very interested in trying them in my lab’s platform,” he said.
Among the key findings of the PLOS study is that the Russian Khosta viruses use the same receptor employed by SARS-CoV-2—known as ACE2—to infect human cells.
“While genetically related to SARS-CoV-2 only distantly, the Russian viruses are most genetically similar to other sarbecoviruses that have been found in Africa and elsewhere in Europe,” Letko said. “For the most part, the specific sarbecovirus group that the Khosta viruses belong to cannot bind on to human ACE2 or infect human cells. Or so we thought.”
He continued: “The receptor used by any virus dictates what tissues the virus infects, which in turn relates to what types of disease symptoms the virus causes and how it transmits between hosts. Because Khosta-2 uses the same human cell receptor as SARS-CoV-2—and SARS-CoV-1, as well as some other seasonal coronaviruses—it may be capable of infecting the same types of cells in humans.”
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Secondly, the researchers found that blood serum from individuals vaccinated against COVID-19 did not neutralize the Khosta-2 virus in laboratory conditions, according to Letko. This was not necessarily surprising.
“One of the standard ways scientists measure the efficacy of a vaccine is with a ‘neutralization assay,'” Letko said. “In this experiment, we combine virus—or in our case, virus-like particles—with serum from people that have received the Moderna or Pfizer vaccines and then add that to cells in test tubes. If antibodies in the serum from the vaccinated person can bind onto the virus, then the virus cannot infect the cells. We can measure that.
“When SARS-CoV-2 gains even a handful of new mutations, we call it a new variant and is generally more vaccine resistant. Because Khosta-2 is so different from SARS-CoV-2, it is not too surprising that the vaccines we use for SARS-CoV-2 cannot effectively stop Khosta-2 from infecting cells,” Letko said.
Thirdly, the team found that infection with the coronavirus’ Omicron variant may not protect against Khosta-2. Serum from people that had recovered from Omicron did not fully neutralize the virus. Again, because Khosta-2 is different enough, the vaccine is not effective.
Letko said it is important to note that in the case of the second and third findings, it is not possible to say with certainty that these responses truly mimic an infection in a real person, given that the results are from cell culture experiments.
“It may be possible that the immune response in a real person would be 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 spark an epidemic or even a pandemic.
“Just because the virus can infect human cells does not mean it will cause a pandemic or even transmit to one single person,” he said. “Many factors control if a virus will transmit and if it will spread between individuals with high efficiency needed for a pandemic.”
Letko continued: “At this point, we do not know the prevalence or likely the true distribution for this virus in nature. As the original scientists who discovered the Khosta viruses noted in their study, [they] are missing genes found in pathogenic human sarbecoviruses that are likely responsible for immune evasion and disease.”
What the researchers are perhaps more concerned about is the potential for a process known as “recombination” to occur.
“We know quite well from the past 40 years of coronavirus research that if two coronaviruses are genetically similar and in the same cell, they can recombine,” Letko said. “Bits of 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 both be called sarbecoviruses and can infect the same cell types using the same mechanisms, it may be possible that they could recombine in a way that would give SARS-CoV-2 the vaccine resistance from Khosta-2 while still retaining other virulence characteristics from SARS-CoV-2.
“The chances of SARS-CoV-2 ever ‘meeting’ Khosta-2 in nature is surely very small, but there have been an increasing number of reports describing SARS-CoV-2 spilling back into wildlife—like white-tailed deer on the East Coast of the United States,” Letko said. “This is all a worst-case scenario but is just one of the things we think about in my lab when trying to keep the next pandemic from happening again.”