So Ray T Y, Lau Kaman K M, Zhou Ziqi, Poon Leo L M, Peiris Malik
School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Division of Infection and Immunity, UCL, London, WC1E 6BT, UK.
bioRxiv. 2025 Jul 1:2025.06.30.662263. doi: 10.1101/2025.06.30.662263.
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus that can cause zoonotic disease in humans with lethal severe viral pneumonia. Dromedary camels are the source of zoonotic infection. As of June 2025, MERS-CoV has resulted in a total of 2626 reported cases, 36% of these being fatal. The number of reported human cases has been on a decreasing trend since 2016 and reached a minimum level during the COVID-19 pandemic. The reason for the reduction of cases is unclear and may be multifactorial. We hypothesized that mutations accumulating in the virus spike protein may have reduced zoonotic potential. Here, we investigate the impact of recently emerged virus spike-protein mutations on virus replication competence using pseudoviruses and replication-competent recombinant viruses. We found that two spike variants detected in 2019 show a reduced cell entry and lower viral replication in human cells. However, spike variants detected in 2023 sequences, did not show significant changes in cell entry and viral replication. All the MERS-CoV spikes tested showed a cell-entry pathway preference via the cell-surface TMPRSS2 route. Our data suggests that spike protein mutations are not a major determinant of the fewer MERS-CoV human cases observed.
中东呼吸综合征冠状病毒（MERS-CoV）是一种新出现的冠状病毒，可在人类中引发人畜共患病，导致致命的严重病毒性肺炎。单峰骆驼是这种人畜共患病感染的源头。截至2025年6月，MERS-CoV已导致共计2626例报告病例，其中36%为致命病例。自2016年以来，报告的人类病例数量呈下降趋势，并在新冠疫情期间降至最低水平。病例减少的原因尚不清楚，可能是多因素的。我们推测，病毒刺突蛋白中积累的突变可能降低了人畜共患病传播潜力。在此，我们使用假病毒和具有复制能力的重组病毒，研究最近出现的病毒刺突蛋白突变对病毒复制能力的影响。我们发现，在2019年检测到的两种刺突变异体在人类细胞中的细胞进入能力降低，病毒复制水平也较低。然而，在2023年序列中检测到的刺突变异体在细胞进入和病毒复制方面未显示出显著变化。所有测试的MERS-CoV刺突蛋白均显示出通过细胞表面TMPRSS2途径的细胞进入途径偏好。我们的数据表明，刺突蛋白突变并非观察到的MERS-CoV人类病例减少的主要决定因素。
