Emerging zoonotic threats: HKU5-CoV-2 and the CBRNE approach to pandemic prevention

Abstract The emergence of HKU5-CoV-2, a novel lineage in the Merbecovirus subgenus, represents a potential zoonotic threat with significant implications for global health. This bat-derived virus, which is phylogenetically similar to the Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2, has demonstrated the ability to use the human angiotensin-converting enzyme 2 receptor to enter human cells. Although no human infections have been reported, its zoonotic potential raises the possibility of spillover events, which could lead to widespread transmission and, under certain conditions, pandemics. This study explores the virological characteristics, epidemiological risks, and clinical implications of HKU5-CoV-2, emphasizing its capacity to cross species barriers and cause severe respiratory diseases. To address the potential for a future pandemic, we propose a theoretical response framework based on the Chemical, Biological, Radiological, Nuclear, and Explosive approach traditionally employed for high-consequence biological threats. This strategy integrates early detection through advanced genomic surveillance, rapid containment measures, the development of targeted medical countermeasures, effective risk communication, and international collaboration. By leveraging lessons from previous coronavirus outbreaks, this framework aims to mitigate the impact of a potential HKU5-CoV-2 spillover and to ensure a coordinated and efficient global response. This study underscores the importance of preparedness in the face of emerging zoonotic viruses and provides a roadmap for managing future biological threats of pandemic potential.