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【施信如 Shih Shin-Ru】【吳弘毅 Wu Hung-Yi】【余冠儀 Yu Guann-Yi】

2025/02/23
Shih Shin-Ru

Executive Director, Research Center for Emerging Viral Infections (BioTReC), Academia Sinica / Chair Professor, Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taiwan. 

Q1: What is HKU5-CoV-2 virus? What are the most important findings of this study?

HKU5-CoV-2 is a bat-derived virus (Merbecovirus) belonging to lineage 2 of HKU5 coronavirus. This virus has some phylogenetic relationship with Middle East Respiratory Syndrome coronavirus (MERS-CoV) but possesses unique genetic characteristics.

The most significant finding of this study is that HKU5-CoV-2 can efficiently use human Angiotensin-Converting Enzyme 2 (ACE2) as a receptor to infect cells. Unlike many other coronaviruses that use ACE2 to enter cells (such as SARS-CoV-2 and NL63), its receptor-binding domain (RBD) binding pattern is completely different. Furthermore, HKU5-CoV-2 demonstrated broad host adaptability, capable of infecting ACE2 receptors from various mammals and successfully infected human cells with ACE2, as well as human respiratory and intestinal organoids. These findings emphasize the virus's potential for cross-species transmission and zoonotic risk.

Q2: What are the limitations of this study's implications? What should we view with caution?

Although the study proved that HKU5-CoV-2 can effectively use human ACE2 receptors to infect cells, three points need to be considered carefully. The study lacks in vivo animal test data, viral infectivity doesn't necessarily indicate effective human-to-human transmission, and environmental infection conditions and intermediate host factors remain undetermined.

Q3: What additional research or scientific evidence is needed to determine HKU5-CoV-2's transmission capability and pathogenicity in humans?

To determine whether HKU5-CoV-2 has the ability to spread between humans and cause disease, the following research and evidence are needed: animal model studies, human serological surveys, viral genome evolution and adaptation studies, environmental viral monitoring, and research on viral replication and immune evasion.

2025/02/24
Wu Hung-Yi

Professor, Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan.

This study examined and analyzed a coronavirus from bats and compared the ability of two viral branches, HKU1 and HKU2, to infect human cells. The study found that like the COVID-19 coronavirus, HKU2 virus binds to the ACE2 receptor on human cells, although the binding mechanism differs from other coronaviruses. Additionally, HKU2 virus shows higher binding capability compared to HKU1.

Since many coronaviruses are discovered in bats, studying bat viruses has its importance and necessity in public health. Continuously discovering and accumulating information about these viruses provides valuable data that can be used to immediately design detection reagents, drugs, or vaccines if a human pandemic occurs.

This study used laboratory-cultured human cells, and it's still unknown whether this virus can actually infect humans or cause a pandemic. To understand and prevent zoonotic diseases, viruses from wildlife need to be studied and monitored carefully. It is recommended that people view this study with caution but not panic.

2025/02/25
Yu Guann-Yi

Associate Investigator, Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Taiwan.

Q1：Why study the HKU5-CoV-2 virus? What are the most important findings of this study?

Some viruses can jump from wildlife to humans, potentially causing severe illness due to limited immune defenses. Bats harbor various viruses that may reach humans through intermediate hosts. For example, Middle East Respiratory Syndrome coronavirus (MERS-CoV) spread from bats to camels and then to humans, exhibiting a high mortality rate. MERS-CoV and bat coronaviruses (HKU4, HKU5) belong to the Merbecoronavirus family and use the DPP4 receptor to infect host cells, highlighting the need for close monitoring of their potential transmission to humans.

HKU5 was previously believed to primarily infect bats with no known link to human infection. However, a recent Cell study reveals that a branch of HKU5 (HKU5-CoV-2) can infect cells using human ACE2 receptors, unlike other Merbecoviruses, which rely on DPP4 for entry. Moreover, HKU5-CoV-2 possesses a furin cleavage site (FCS)—a key feature of SARS-CoV-2—known to enhance viral entry efficiency, suggesting that some bat coronaviruses may directly infect human cells.

This study highlights the potential cross-species infection risks of understudied coronaviruses, underscoring the need to monitor bat virus evolution continuously.

Q2：What are the limitations of this study's implications? What should we view with caution?

This study, based solely on cell experiments, demonstrates that HKU5-CoV-2 can use ACE2 to infect human cells but does not confirm its infectivity, pathogenicity, or transmissibility in animals or humans. It does not indicate that the virus can effectively infect and spread in the general population. Vigilance is required, but there is no need for panic.

Q3：What additional research or scientific evidence is needed to understand HKU5-CoV-2 virus's transmission and pathogenic capabilities in humans?

To assess whether HKU5-CoV-2 poses a risk to humans, live virus testing in animals is essential, including transgenic mice with human ACE2 receptors and primates, to evaluate its pathogenicity and transmission potential. If the virus exhibits high infectivity and transmissibility in other species, further research should investigate its prevalence in bats or other animal hosts and assess any past human infections.

Currently, no evidence suggests that HKU5-CoV-2 can effectively transmit or cause disease in humans. The findings should not be overinterpreted, and further rigorous animal and clinical studies are needed to determine the actual risks.