Wang Chao, Huang Yi-Man, Zhao Jun, Bai Yi-Ming, Yan Cai-Qin, Du Guan-Hua, Zheng Li-Shu, Liu Ai-Lin
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Beijing Key Lab of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Front Cell Infect Microbiol. 2024 Dec 24;14:1484245. doi: 10.3389/fcimb.2024.1484245. eCollection 2024.
Respiratory syncytial virus (RSV) remains a major international public health concern. However, disease treatment is limited to preventive care with monoclonal antibodies and supportive care. In this study, natural products were screened to identify novel anti-RSV inhibitors.
The antiviral effect of 320 compounds on RSV in HEp-2 cells was tested using a Cytopathic effect (CPE) inhibition assay. The antiviral effect of fumarprotocetraric acid (FUM) and geraniin (GE) were confirmed by Real-time reverse transcription quantitative PCR (Real-time RT-PCR), plaque reduction test, immunofluorescence assay, and Western blot analysis. Real-time PCR was used to detect inflammatory factor expression. ATP assay and JC-1 stain were used to evaluate mitochondrial protection function. The experiment of administration time was used to determine the stages in the RSV life cycle inhibited by FUM and GE. Human metapneumovirus (HMPV) and human rhinovirus (HRV) were used to evaluate the antiviral activities of other respiratory viruses of FUM and GE. Finally, Air-liquid interface human airway epithelium (ALI-HAE) cells were used to evaluate the antiviral effect and mechanism of FUM and GE to RSV.
The results showed that FUM and GE can inhibit the replication of RSV in multiple-cell models. Both compounds could dose-dependent inhibit the viral load, RSV nucleic acids level, and RSV-F protein level. Besides, FUM and GE showed good anti-inflammatory activity, mitochondrial protection, and antiviral activity to HMPV and HRV. Meanwhile, our result indicated that FUM and GE can inhibit RSV replication in ALI-HAE cells.
FUM and GE were identified as new inhibitors of RSV infection. At the same time, FUM and GE have anti-inflammatory activity, mitochondrial protection function, and broad-spectrum antiviral activity. These results provide evidence that FUM and GE are potential candidates for the development of novel anti-RSV drugs.
呼吸道合胞病毒（RSV）仍然是一个重大的国际公共卫生问题。然而，疾病治疗仅限于使用单克隆抗体的预防性护理和支持性护理。在本研究中，对天然产物进行筛选以鉴定新型抗RSV抑制剂。
使用细胞病变效应（CPE）抑制试验检测320种化合物对HEp-2细胞中RSV的抗病毒作用。通过实时逆转录定量PCR（实时RT-PCR）、蚀斑减少试验、免疫荧光测定和蛋白质免疫印迹分析证实了富马原岛衣酸（FUM）和老鹳草素（GE）的抗病毒作用。使用实时PCR检测炎症因子表达。采用ATP检测和JC-1染色评估线粒体保护功能。给药时间实验用于确定FUM和GE抑制RSV生命周期的阶段。使用人偏肺病毒（HMPV）和人鼻病毒（HRV）评估FUM和GE对其他呼吸道病毒的抗病毒活性。最后，使用气液界面人呼吸道上皮（ALI-HAE）细胞评估FUM和GE对RSV的抗病毒作用及其机制。
结果表明，FUM和GE可在多种细胞模型中抑制RSV复制。这两种化合物均可剂量依赖性地抑制病毒载量、RSV核酸水平和RSV-F蛋白水平。此外，FUM和GE对HMPV和HRV表现出良好的抗炎活性、线粒体保护作用和抗病毒活性。同时，我们的结果表明FUM和GE可抑制ALI-HAE细胞中RSV的复制。
FUM和GE被鉴定为RSV感染的新型抑制剂。同时，FUM和GE具有抗炎活性、线粒体保护功能和广谱抗病毒活性。这些结果证明FUM和GE是开发新型抗RSV药物的潜在候选物。
