People who recovered from COVID-19 infection or were vaccinated against SARS-CoV-2 are more likely to have immunity to other closely related bat coronaviruses that could have the potential to threaten future human health.
In a joint study by The Pirbright Institute and King's College London (KCL), scientists found bat coronaviruses most likely to infect a wide range of animal species are those most closely related to SARS-CoV-2 and most likely to be recognised by immunity generated through COVID-19 infection.
The research, funded by the Biotechnology and Biological Sciences Research Council (UK Research and Innovation - UKRI), Wellcome, and the Medical Research Council (MRC - part of UKRI), is published today in two companion articles in PLOS Biology .
Researchers examined how a diverse group of bat sarbecoviruses - the coronavirus sub-group that includes SARS-CoV-1 and SARS-CoV-2 - interact with ACE2, the cellular receptor used by many coronaviruses to enter host cells.
They investigated the ability of these viruses to use ACE2 proteins from a broad range of bat and mammalian species, including humans, livestock, rodents and animals previously proposed as intermediate hosts.
The team discovered so-called "generalist" sarbecoviruses, which can use ACE2 receptors from many different species, were largely confined to the same evolutionary group as SARS-CoV-2.
Pirbright postdoctoral scientist and lead author, Dr Nazia Thakur , said: "Our findings suggest that the bat coronaviruses currently considered most likely to spill over into humans are also most likely to be recognised by existing COVID-19 immunity. While spillover risk can never be eliminated, widespread exposure to SARS-CoV-2 may have raised the barrier for related viruses to establish themselves in human populations."
The team analysed 15 representative bat coronavirus spike proteins using libraries of ACE2 receptors from 34 species. Broad ACE2 usage was a defining feature of viruses closely related to SARS-CoV-2, including the BANAL viruses discovered in Laos. Viruses from other evolutionary groups, including a novel UK bat coronavirus RhGB07, showed more restricted receptor usage. To aid in their analyses the Spike structure of RhGB07 was also resolved by collaborators in Switzerland.
The study also investigated how SARS-CoV-2 host range has evolved during the pandemic. Researchers found variants, particularly those within the Omicron lineage acquired mutations in the receptor binding domain which resulted in shifting patterns of ACE2 usage across animal species, highlighting the dynamic relationship between viral evolution and host susceptibility.
To understand the implications for human health, the scientists examined blood samples from people who had recovered from COVID-19. Antibodies in these samples successfully neutralised a range of closely related bat coronaviruses. Importantly, researchers also detected lower levels of neutralisation against more distant bat sarbecoviruses, suggesting some degree of broader protection.
Katie Doores , Professor of Viral Immunology at KCL, said, "These viruses showed the strongest antigenic similarity to SARS-CoV-2, meaning they were more readily recognised and neutralised by antibodies generated following COVID-19 infection. In contrast, more distantly related bat coronaviruses tended to be "specialists", capable of using ACE2 receptors from only a limited range of hosts."
Further experiments at KCL and Pirbright identified several monoclonal antibodies capable of recognising a remarkably diverse range of sarbecoviruses. The second companion article identified where these monoclonal antibodies bind, highlighting conserved regions of the coronavirus spike protein, and offering important clues for the development of next-generation vaccines and therapeutics.
Dr Dalan Bailey , head of Pirbright's Viral Glycoproteins group, added: "One of the encouraging findings was evidence of cross-neutralisation of even some of the more distantly related bat coronaviruses. This suggests that broadly protective, pan-sarbecovirus vaccines or therapeutics may be achievable."
The work highlights the importance of understanding virus host range, receptor usage and immune recognition together rather than in isolation. By identifying characteristics that distinguish higher-risk viruses from those less likely to spill over into humans, researchers hope to strengthen global pandemic preparedness efforts.
