Doki Tomoyoshi, Shinohara Kazuki, To Kaito, Takano Tomomi
Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada 034-8628, Aomori, Japan.
Pathogens. 2025 Aug 7;14(8):787. doi: 10.3390/pathogens14080787.
The cross-species spillover of coronaviruses is considered a serious public health risk. Feline coronavirus (FCoV), canine coronavirus (CCoV), and transmissible gastroenteritis virus (TGEV) are all classified under and infect companion animals and livestock. Due to their frequent contact with humans, these viruses pose a potential risk of future cross-species transmission. Molnupiravir, a prodrug of N4-hydroxycytidine, exhibits potent antiviral activity against SARS-CoV-2, a member of the genus, and has been approved for the treatment of COVID-19. Molnupiravir was recently shown to be effective against FCoV, suggesting broad-spectrum antiviral activity across coronavirus lineages. Based on these findings, the present study investigated whether molnupiravir is also effective against CCoV and TGEV, which belong to the same species as FCoV. We examined the in vitro antiviral effects of molnupiravir using four viral strains: FCoV-1 and -2, CCoV-2, and TGEV. Molnupiravir inhibited plaque formation, viral antigen expression, the production of infectious viral particles, and viral RNA replication in a dose-dependent manner in all strains. IC values for CCoV-2 and TGEV, calculated using a feline-derived cell line (fcwf-4), were significantly lower than those for FCoV, suggesting higher sensitivity to molnupiravir. These results demonstrate that molnupiravir exhibited broad antiviral activity against animal coronaviruses classified under , providing a foundation for antiviral strategies to mitigate the future risk of cross-species transmission.
冠状病毒的跨物种传播被认为是严重的公共卫生风险。猫冠状病毒（FCoV）、犬冠状病毒（CCoV）和传染性胃肠炎病毒（TGEV）都属于同一类别，可感染伴侣动物和家畜。由于它们与人类频繁接触，这些病毒构成了未来跨物种传播的潜在风险。莫努匹拉韦是N4-羟基胞苷的前药，对β属成员严重急性呼吸综合征冠状病毒2（SARS-CoV-2）具有强大的抗病毒活性，已被批准用于治疗2019冠状病毒病（COVID-19）。最近研究表明莫努匹拉韦对猫冠状病毒有效，提示其对冠状病毒谱系具有广谱抗病毒活性。基于这些发现，本研究调查了莫努匹拉韦对与猫冠状病毒属于同一物种的犬冠状病毒和传染性胃肠炎病毒是否也有效。我们使用四种病毒株：猫冠状病毒-1和-2、犬冠状病毒-2和传染性胃肠炎病毒，检测了莫努匹拉韦的体外抗病毒作用。莫努匹拉韦在所有毒株中均以剂量依赖性方式抑制空斑形成、病毒抗原表达、传染性病毒颗粒的产生和病毒RNA复制。使用猫源细胞系（fcwf-4）计算得出的犬冠状病毒-2和传染性胃肠炎病毒的半数抑制浓度（IC）值显著低于猫冠状病毒，表明对莫努匹拉韦的敏感性更高。这些结果表明，莫努匹拉韦对属于同一类别的动物冠状病毒具有广泛的抗病毒活性，为减轻未来跨物种传播风险的抗病毒策略奠定了基础。
