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Background:
Taiwan media reported on a study published in Cell journal on the 18th of this month, revealing that Chinese researchers discovered that HKU5-CoV-2 coronavirus, like SARS-CoV-2 (which causes COVID-19), contains a feature called "furin cleavage site" and can enter cells through the ACE2 receptor protein on human cell surfaces.
Having experienced the global COVID-19 pandemic, this coronavirus study has raised concerns among many people on social media in Taiwan. The Science Media Center Taiwan invited experts to comment on this research.
Resarch paper:Bat-infecting merbecovirus HKU5-CoV lineage 2 can use human ACE2 as a cell entry receptor
Expert reaction:
【施信如 Shih Shin-Ru】【吳弘毅 Wu Hung-Yi】
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.
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.
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