Researchers at WSU have found that a sarbecovirus discovered in Russian lesser horseshoe bats is capable of infecting humans and is resistant to the antibodies of people vaccinated against SARS‑CoV‑2.
After initially appearing harmless to humans, researchers at Washington State University (WSU) have now discovered a coronavirus found in Russian bats in 2020 does indeed have the potential to spillover to humans, and it is resistant to SARS-CoV-2 antibodies and vaccination.
In late 2020, researchers identified two clade 3 sarbecoviruses—the same sub-category of coronaviruses SARS-CoV-2 belongs to—in Rhinolophus bats in Russia. Clade 3 viruses, as distinguished by virologists, are found more widely in African and European bats, contain one deletion and primarily infect using bat ACE2—the same receptor SARS-CoV-2 exploits.
The two new viruses, dubbed Khosta-1 and Khosta-2, initially appeared non-threatening to humans as they are genetically distinct from human SARS-CoVs in that they lack genetic information encoding for some of the genes thought to antagonize the immune system and contribute to pathogenicity. In fact, these two viruses looked like hundreds of other sarbecoviruses discovered in recent years, predominantly in bats in Asia, that are not capable of infecting human cells.
Taking a closer look at Khosta-2, however, the Washington State University team saw a different story.
“When we looked at them more, we were really surprised to find they could infect human cells. That changes a little bit of our understanding of these viruses, where they come from and what regions are concerning,” said corresponding author Michael Letko, a WSU virologist.
The study, published in PLoS Pathogens, shows that like SARS-CoV-2, Khosta-2 can use its spike protein to infect cells by attaching to the receptor ACE2 (angiotensin converting enzyme 2), which is found throughout human cells.
With that knowledge, the researchers next tested whether SARS-CoV-2 antibodies had any effect on Khosta-2. Using serum derived from human populations vaccinated for COVID-19, the team saw that Khosta-2 was not neutralized by current vaccines. They also tested serum from those infected with the Omicron variant, but those antibodies, too, were ineffective.
Letko said the discovery of Khosta-2 highlights the need to develop universal vaccines to protect against sarbecoviruses in general, rather than just against known variants of SARS-CoV-2. Even among current universal sarbecovirus vaccines in development, most include clade 1 viruses and one of the clade 2 viruses, but do not include any members from clade 3.
“Right now, there are groups trying to come up with a vaccine that doesn’t just protect against the next variant of SARS-2 but actually protects us against the sarbecoviruses in general,” he said. “Unfortunately, many of our current vaccines are designed to specific viruses we know infect human cells or those that seem to pose the biggest risk to infect us. But that is a list that’s ever-changing. We need to broaden the design of these vaccines to protect against all sarbecoviruses.”
Even though Khosta-2 lacks some of the genes believed to be involved in SARS-CoV-2 pathogenesis in humans, the virus poses a risk of recombining with a second virus—like SARS-CoV-2.
“When you see SARS-2 has this ability to spill back from humans and into wildlife, and then there are other viruses like Khosta-2 waiting in those animals with these properties we really don’t want them to have, it sets up this scenario where you keep rolling the dice until they combine to make a potentially riskier virus,” said Letko.