Study Reveals Bat Viruses Closely Related to MERS Could Mutate to Infect Humans

A recent study published in Nature Communications has identified a group of bat viruses called merbecoviruses, which include the deadly Middle East respiratory syndrome coronavirus (MERS-CoV), as potential threats to human health. The research, conducted by scientists from Washington State University (WSU), the California Institute of Technology, and the University of North Carolina, particularly focussed on a subgroup of merbecoviruses known as HKU5. These viruses share concerning traits that suggest they could be just a single mutation away from infecting humans and triggering a new pandemic. Over the past two decades, the genetic sequences of thousands of viruses in wild animals have been catalogued, but many remain under-studied due to the lack of evidence that they pose immediate danger to humans. Michael Letko, a virologist at WSU's College of Veterinary Medicine, aims to bridge this knowledge gap by identifying potentially zoonotic viruses. His team’s focus on merbecoviruses stems from the fact that MERS-CoV, a virus within this subgenus, is known to cause severe respiratory disease in humans, transmitted primarily from dromedary camels. MERS-CoV has a mortality rate of about 34%, making it a highly lethal pathogen. Coronaviruses, including merbecoviruses, use a spike protein to bind to receptors on host cells and gain entry. To investigate this process, Letko's team created virus-like particles containing only the spike protein segment responsible for receptor binding. They then tested these particles in the lab to determine their ability to infect different types of cells. Most merbecoviruses appeared unlikely to infect human cells, but the HKU5 subgroup stood out. HKU5 viruses, found globally in various bat species, can bind to the ACE2 receptor, which is the same receptor used by the SARS-CoV-2 virus that causes COVID-19. However, unlike SARS-CoV-2, HKU5 currently binds to the ACE2 gene in bats much more effectively than in humans. The researchers identified specific mutations in the spike protein of HKU5 viruses that could enhance their ability to bind to human ACE2 receptors. This finding underscores the virus's potential to cross the species barrier. For instance, an earlier study revealed that an HKU5 virus in China had already infected minks, indicating its capacity to jump from one species to another. Letko emphasized the importance of monitoring these viruses, given their close relationship to MERS-CoV. While there is currently no evidence that HKU5 has infected humans, the genetic similarity and the potential for mutations mean that they should be closely watched. To understand the molecular interactions between the HKU5 spike protein and the ACE2 receptor, the team employed artificial intelligence (AI) using the AlphaFold 3 program. Postdoctoral researcher Victoria Jefferson at WSU generated accurate models of these interactions within minutes, a process that traditionally requires months of lab work and specialized equipment. The AI-generated results were validated by another research team that used conventional methods, demonstrating the potential of AI in accelerating viral research and drug development. The study's findings highlight the ongoing risk posed by emerging viruses and the need for continued surveillance and preparedness. By identifying the specific mutations that could enable HKU5 to infect humans, the research provides crucial insights for developing strategies to prevent or mitigate a potential outbreak. Letko suggests that these methods could be applied to other virology studies, aiding in the rapid identification and characterization of new viral threats. Industry insiders have praised the study for its innovative use of AI in virology research, noting that such tools could significantly speed up the discovery of new vaccines and treatments. Companies like WSU, known for its leading research in veterinary medicine and global health, play a critical role in advancing scientific understanding and public health initiatives. The ability to quickly predict viral behavior and receptor binding is seen as a major step forward in preparing for future pandemics, making the findings both scientifically valuable and practically applicable.