From Bats to Humans: How HKU5 Virus Could Be the Next COVID-19 or MERS

HKU5 Virus: The Bat Borne Threat Just One Mutation Away from a Global Pandemic

Scientists Identify Bat Virus Just One Mutation Away from Causing the Next Pandemic

• A recent study published in Nature Communications has raised significant concerns about a group of bat viruses, specifically the HKU5 subgroup, which are closely related to the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

• Researchers from Washington State University, the California Institute of Technology, and the University of North Carolina have found that these viruses possess the ability to bind to the ACE2 receptor which is a key entry point for SARS-CoV-2 suggesting that they could potentially infect humans with just a single mutation. This discovery underscores the risk of zoonotic spillover, where viruses jump from animals to humans, potentially leading to a global pandemic.

• Zoonotic refers to diseases that are naturally transmissible between vertebrate animals and humans. These diseases can be caused by pathogens such as viruses, bacteria, fungi, and parasites. For example, ebola, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome coronavirus (MERS-CoV), COVID-19, H5N1 avian influenza flu or bird flu are zoonotic diseases.

• MERS-CoV is transmitted from camels to humans. A prospective genome study showed that MERS-CoV was present in 22.8% of the camels that the researchers sampled, it demonstrated that MER-CoV could be potential occupational hazards to camel shepherds.

What Are Merbecoviruses?

• Merbecoviruses are a subgenus of coronaviruses that includes MERS-CoV, which was first identified in 2012 and has a mortality rate of approximately 34%. These viruses primarily infect bats but have the potential to jump to humans, as evidenced by MERS-CoV. While most merbecoviruses have been studied to some extent, the HKU5 subgroup has received limited attention until now.

The Discovery of HKU5's Potential to Infect Humans

• The recent study focused on understanding how HKU5 viruses infect host cells. The researchers found that while most merbecoviruses appear unlikely to pose a direct threat to humans, HKU5 viruses possess concerning traits.

• Specifically, HKU5 viruses were shown to use a host receptor known as ACE2, the same receptor used by the more well-known SARS-CoV-2 virus that causes COVID-19. For now HKU5 viruses can only use the ACE2 gene in bats and do not use the human version nearly as well.

• This discovery is significant because it suggests that with just a small mutation, HKU5 viruses could potentially infect humans. The researchers used artificial intelligence to model how the HKU5 spike protein binds to ACE2 at the molecular level, which could help provide a better understanding of how antibodies might block the infection or how the virus could mutate.

The Risk of Zoonotic Spillover

• Zoonotic spillover refers to the process by which a virus jumps from animals to humans. This has been the source of several past pandemics, including SARS, MERS, and COVID-19. The ability of HKU5 viruses to bind to the ACE2 receptor in bats and potentially in humans raises the possibility of zoonotic spillover.

• The study also highlighted that one HKU5 virus in China has already been documented to have jumped into minks, showing there is potential for interspecies transmission.

Conclusion

• While there are no confirmed human infections at this time, the findings highlight the need for preparedness and vigilance in monitoring emerging zoonotic threats.

• The use of artificial intelligence in modeling virus receptor interactions is also noted as a valuable tool in understanding and mitigating potential risks. Continued surveillance and research are essential to prevent future pandemics linked to emerging viruses.

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References

Chen J, Zhang & et al. Bat-infecting merbecovirus HKU5-CoV lineage 2 can use human ACE2 as a cell entry receptor. Cell. 2025 Mar 20;188(6):1729-1742.e16.

Catanzaro NJ & et al. ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses. Nat Commun. 2025 May 28;16(1):4932.

Azhar EI & et al. The Middle East Respiratory Syndrome (MERS). Infect Dis Clin North Am. 2019 Dec;33(4):891-905.

El-Kafrawy SA & et al. Enzootic patterns of Middle East respiratory syndrome coronavirus in imported African and local Arabian dromedary camels: a prospective genomic study. Lancet Planet Health. 2019 Dec;3(12):e521-e528.

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