A virus called Khosta-2, found in Russian horseshoe bats, is capable of using ACE2—the same receptor used by SARS-CoV-2—to enter human cells, researchers have found. Interestingly, the virus is resistant to neutralization by the antibodies of people vaccinated against SARS-CoV-2.

However, the likelihood that Khosta-2 might cause disease in humans is unknown. “Just because the virus can infect human cells does not mean it will cause a pandemic or even transmit to one single person,” Michael Letko, PhD, told GEN.

Letko, who led the study, is an assistant professor at Washington State University. His team published their findings in PLoS Pathogens in the article entitled “An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines.”

“This work is part of a larger effort from my lab to characterize zoonotic properties of new viruses as they are discovered,” Letko explained. Khosta-2 is one of hundreds of sarbecoviruses that have been identified, mainly in bats in Asia. The virus behind the COVID-19 pandemic, SARS-CoV-2, is also a sarbecovirus.

Most sarbecoviruses are not capable of infecting human cells, but occasional transmission from bats to humans or other animals does occur.

“Khosta-2 was discovered in one [non-bat] animal in 2021,” Letko explained. “To my knowledge, it has not been found again in any other animal or humans. To be fair, though, there are not a ton of researchers looking for sarbecoviruses [in non-bat animals] in Russia at the moment.”

In addition to Khosta-2, Letko’s team examined Khosta-1, a sarbecovirus from the greater horseshoe bat, Rhinolophus ferrumequinum. Khosta-2 is from the lesser horseshoe bat, R. hipposideros.

“The Khosta-1 RBD [receptor binding domain] failed to infect cells expressing any of the human receptors, while Khosta-2 RBD clearly infected cells expressing human ACE2,” the researchers wrote in their article.

In addition, they found that Khosta-2 RBDs were resistant to SARS-CoV-2 monoclonal antibodies and to serum from omicron-infected individuals. “These findings are not too surprising given that the Khosta-2 RBD only shares about 60% sequence identity with [that of] SARS-CoV-2,” they wrote, “and the neutralizing antibodies elicited by the vaccines from Moderna or Pfizer are directed primarily toward the RBD.”

But the researchers say that their findings underscore the need to develop vaccines with broader protection against the sarbecoviruses.

“SARS-CoV-2 is just one member in a group of viruses that have wide geographic distribution and potential to infect humans,” Letko pointed out. “We should avoid over-generalizing these viruses as ‘Asian’ or even strictly ‘bat.’ If there ever is a SARS-CoV-3, it could emerge outside of China.”

The Khosta sarbecoviruses are missing some of the genes in SARS-CoV-2 that are thought to be responsible for antagonizing the immune system and causing COVID-19. So Khosta-2 may not cause disease, even if it spreads from bats to humans.

“What we are maybe more concerned about is recombination,” Letko explained. “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 they could recombine in a way that would give SARS-CoV-2 the vaccine-resistance from Khosta-2 while still retaining other SARS-CoV-2 virulence factors.

“The chances of SARS-CoV-2 ever ‘meeting’ Khosta-2 in nature is surely very small,” he continued. “This is all a worst-case scenario but is just one of things we think about in my lab when trying to keep then next pandemic from happening again.”

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