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| Professor Alan Wong Siu-lun (centre), from the School of Biomedical Sciences at HKUMed, leads a dynamic multidisciplinary research team comprising experts in medicine and engineering. Together, they pioneer groundbreaking method for the swift identification of SARS-CoV-2 mutations. |
A collaborative effort between the LKS Faculty of Medicine (HKUMed) and the Faculty of Engineering at the University of Hong Kong (HKU) has yielded a groundbreaking screening platform designed to swiftly evaluate the impact of SARS-CoV-2 mutations on disease severity. This innovative platform, detailed in a publication in Nature Biomedical Engineering, showcases a remarkable speed improvement of up to 39 times compared to conventional methods. Notably, the research team focused on understanding how mutations influence syncytium formation, a process crucial for the fusion of infected and uninfected cells, shedding light on emerging viral variants that could pose significant public health risks. Moreover, the team identified two FDA-approved drugs capable of mitigating disease severity, further underscoring the practical implications of their findings.
Background: Since its emergence, the SARS-CoV-2 virus has been undergoing continuous evolution, with spike protein mutations potentially affecting infectivity and lethality. Recognizing the spike protein's pivotal role in viral infection, researchers have delved into understanding how mutations influence syncytium formation, a process associated with disease severity, particularly in severe COVID-19 cases.
Research Findings: Employing a novel screening method integrating split green fluorescent protein (GFP) and microfluidics-based technology, the research team achieved unprecedented efficiency in assessing a wide range of spike protein variants and their fusion capabilities. Their investigation revealed that certain variants, notably the Delta strain, exhibited enhanced syncytium formation compared to the original strain. Additionally, they pinpointed specific mutations, such as K854H in the Omicron variant, that significantly altered fusion rates, underscoring the importance of monitoring emerging mutations. Notably, the team's innovative screening approach facilitated the identification of two FDA-approved drugs, chlorpromazine and fluvoxamine, capable of inhibiting syncytium formation and potentially alleviating disease severity.
Significance of the Study: The interdisciplinary approach employed in this study, combining high-throughput CRISPR screening, large-scale mutagenesis, droplet microfluidics, and virology, holds significant promise for understanding and combating SARS-CoV-2 and other diseases involving cell fusion. Notably, the study's findings provide valuable insights into therapeutic interventions for COVID-19 and other pathologies associated with syncytium formation.
Moving forward: The research team's findings offer promising avenues for public health interventions and therapeutic development, with potential applications extending beyond COVID-19 to various pathological and physiological conditions involving cell fusion. The methods and insights derived from this study hold considerable potential for advancing biomedical research and improving health outcomes.
About the Research Team: Led by Professor Alan Wong Siu-lun and Dr. Gigi Choi Ching-gee from HKUMed, along with Professor Chu Hin from the Department of Microbiology, School of Clinical Medicine, HKUMed, and Professor Anderson Shum Ho-cheung from the Faculty of Engineering, the collaborative research team comprises a diverse group of experts spanning multiple disciplines.
Acknowledgments: The research was made possible through support from various funding sources, including the National Natural Science Foundation of China and the Hong Kong Research Grants Council's Collaborative Research Fund.
For media inquiries, please contact the LKS Faculty of Medicine of The University of Hong Kong via email (medmedia@hku.hk).
* This article was originally published here
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