Scientists Warn HKU5 Bat Viruses Could Be One Mutation Away From Human Infection

Scientists Warn HKU5 Bat Viruses Could Be One Mutation Away From Human Infection A groundbreaking study published in Nature Communications has raised urgent concerns about a group of bat coronaviruses that may require only minimal genetic changes to infect humans. The research, conducted by an international team from Washington State University, California Institute of Technology, and the University of North Carolina, focuses on HKU5 merbecoviruses—a subgroup of coronaviruses closely related to the deadly Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

The study reveals that HKU5 viruses, which naturally infect Japanese house bats (Pipistrellus abramus), have demonstrated the ability to bind to ACE2 receptors in bats—the same cellular entry point that SARS-CoV-2 uses to infect human cells. While these viruses cannot yet efficiently bind to human ACE2 receptors, researchers have identified specific spike protein mutations that could enable cross-species transmission. This discovery is particularly concerning given that MERS-CoV, a closely related virus in the same subgroup, carries a case fatality rate of approximately 36 percent according to World Health Organization data, with 2,626 laboratory-confirmed cases and 947 associated deaths reported globally since April 2012.

The research team employed sophisticated laboratory techniques to understand the viral mechanisms involved in host cell infection. Scientists engineered virus-like particles containing receptor-binding domains from HKU5 spike proteins to test their interaction with various host cell receptors. The results demonstrated that while HKU5 viruses can effectively use bat ACE2 receptors, they have limited efficiency with human ACE2. However, the study identified concerning mutations in the spike proteins that could potentially bridge this species barrier.

One of the most alarming findings involves evidence that HKU5 viruses are already showing signs of host-jumping capability. Researchers documented cases where HKU5 viruses have successfully infected minks in China, demonstrating that these pathogens are actively evolving to expand their host range. This cross-species transmission pattern mirrors the evolutionary pathway that led to previous coronavirus outbreaks, including SARS and COVID-19, both of which originated from bat reservoirs before adapting to infect humans.

The study leveraged cutting-edge artificial intelligence technology to accelerate the research process significantly. PhD researcher Victoria Jefferson from Washington State University utilized AlphaFold3, an advanced AI-based protein prediction tool, to model the interaction between HKU5 spike proteins and ACE2 receptors. This innovative approach compressed what would traditionally require months of laboratory work into a matter of minutes, providing rapid confirmation of experimental findings and revealing the precise structural changes that could enable human infection.

Geographic distribution data indicates that HKU5 viruses have been detected across multiple continents, including Asia, Africa, Europe, and the Middle East, suggesting a widespread presence in bat populations globally. The viruses originate primarily from Japanese house bats, but their broad geographic range increases the potential for human contact and subsequent spillover events. This distribution pattern is particularly significant given the increasing encroachment of human activities into natural habitats where these bat populations reside.

Dr. Michael Letko, who led the research team at Washington State University, emphasized the preventive nature of this surveillance work. He noted that while HKU5 viruses have not yet infected humans, the similarities to MERS-CoV warrant careful monitoring and preparedness measures. The research underscores the importance of proactive viral surveillance, particularly for coronaviruses with demonstrated pandemic potential.

Recent complementary research published in the journal Cell has identified a distinct lineage called HKU5-CoV-2 that shows even greater efficiency in utilizing human ACE2 receptors. This discovery, reported by researchers at China's Wuhan Institute of Virology, further validates concerns about the zoonotic potential of these viral lineages. The combined findings from multiple research groups worldwide highlight the urgent need for enhanced monitoring systems and preparedness strategies for potential coronavirus spillover events.

The implications of this research extend beyond immediate public health concerns to broader questions about pandemic preparedness and viral surveillance systems. The study demonstrates how modern biotechnology, including AI-driven protein modeling, can accelerate threat assessment and provide early warning systems for emerging viral diseases. These technological advances represent crucial tools for identifying potential pandemic pathogens before they acquire full human transmission capability.

Expert commentary from the London School of Hygiene and Tropical Medicine notes that while the discovery of HKU5-CoV-2's ability to use human ACE2 receptors is concerning, the research provides valuable insights for pandemic preparedness efforts. The findings emphasize the ongoing need for comprehensive surveillance of bat coronavirus populations and continued investment in rapid response capabilities for emerging viral threats.

The research was supported by data from comprehensive coronavirus surveillance programs across Asia, which have documented the extensive genetic diversity of bat coronaviruses. These surveillance efforts have revealed that bats harbor the highest proportion of genetically diverse coronaviruses among mammalian species, making them a critical focus for zoonotic disease monitoring. The current findings add to a growing body of evidence suggesting that multiple bat coronavirus lineages may pose spillover risks to human populations.