Liu Feng, Shang Chao, Zhang Cheng, Jiang Xuyong, Lin Yanling, Wu Fushan, Li Jingxuan, Han Lu, Shan Junjie, Xiao Zhiyong, Zhou Wenxia
Beijing Institute of Pharmacology & Toxicology, Beijing 100850, China; State Key Laboratory of National Security Specially Needed Drug, Beijing Institute of Pharmacology & Toxicology, Beijing 100850, China.
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CASS), Changchun 130122, China.
Int J Biol Macromol. 2025 May;307(Pt 4):142233. doi: 10.1016/j.ijbiomac.2025.142233. Epub 2025 Mar 17.
Polysaccharides derived from Traditional Chinese Medicine (TCM) show potential as therapeutic agents in the treatment of viral infections. In this study, seventeen polysaccharides extracted from TCM were screened for their inhibitory effects on SARS-CoV-2 pseudovirus (PsV) infection in ACE2-overexpressing HEK293T cells. The results revealed that Cnidii fructus polysaccharides (CFPs) and Sophorae Flavescentis Radix polysaccharides (SFPs) significantly inhibited PsV entry. Then, the effects of CFPs and SFPs on the authentic SARS-CoV-2 virus were studied. We found that CFPs and SFPs significantly inhibited cellular damage and virus invasion induced by both the Original SARS-CoV-2 strain and the Omicron variant in Vero E6 cells, without causing obvious cytotoxicity. In vivo studies demonstrated that CFPs and SFPs significantly protect mice against SARS-CoV-2 virus-induced mortality, along with reductions in viral load and lung injury. Time of addition (TOA) experiments indicated that CFPs and SFPs exert inhibitory effects during the pseudoviral pre-attachment and cell entry stages, with no substantial impacts after the PsV has entered the cells. Further mechanism studies showed that CFPs and SFPs inhibited syncytial formation primarily by suppressing the host cell surface membrane fusion process mediated by the Spike protein, without significantly affecting the endosome-mediated viral entry.
源自中药的多糖在治疗病毒感染方面显示出作为治疗剂的潜力。在本研究中，筛选了从中药中提取的17种多糖对过表达ACE2的HEK293T细胞中SARS-CoV-2假病毒（PsV）感染的抑制作用。结果显示，蛇床子多糖（CFPs）和苦参多糖（SFPs）显著抑制PsV进入。然后，研究了CFPs和SFPs对真实SARS-CoV-2病毒的作用。我们发现，CFPs和SFPs显著抑制了原始SARS-CoV-2毒株和奥密克戎变体在Vero E6细胞中诱导的细胞损伤和病毒入侵，且未引起明显的细胞毒性。体内研究表明，CFPs和SFPs显著保护小鼠免受SARS-CoV-2病毒诱导的死亡，同时降低病毒载量和肺损伤。添加时间（TOA）实验表明，CFPs和SFPs在假病毒预附着和细胞进入阶段发挥抑制作用，在PsV进入细胞后没有实质性影响。进一步的机制研究表明，CFPs和SFPs主要通过抑制由刺突蛋白介导的宿主细胞表面膜融合过程来抑制合胞体形成，而对内涵体介导的病毒进入没有显著影响。
