褐藻糖胶
硫酸乙酰肝素
病毒
硫酸化
多糖
微生物学
化学
生物
体内
药理学
肝素
病毒学
生物化学
生物技术
作者
Yu Song,Amit Kumar Singh,Maisha M. Feroz,Shirley Xu,Fuming Zhang,Weihua Jin,Amrendra Kumar,Parastoo Azadi,Dennis W. Metzger,Robert J. Linhardt,Jonathan S. Dordick
标识
DOI:10.1016/j.carbpol.2024.122156
摘要
Seaweeds represent a rich source of sulfated polysaccharides with similarity to heparan sulfate, a facilitator of myriad virus host cell attachment. For this reason, attention has been drawn to their antiviral activity, including the potential for anti-SARS-CoV-2 activity. We have identified and structurally characterized several fucoidan extracts, including those from different species of brown macroalga, and a rhamnan sulfate from a green macroalga species. A high molecular weight fucoidan extracted from Saccharina japonica (FSjRPI-27), and a rhamnan sulfate extracted from Monostroma nitidum (RSMn), showed potent competitive inhibition of spike glycoprotein receptor binding to a heparin-coated SPR chip. This inhibition was also observed in cell-based assays using hACE2 HEK-293 T cells infected by pseudotyped SARS-CoV-2 virus with IC50 values <1 μg/mL. Effectiveness was demonstrated in vivo using hACE2–transgenic mice. Intranasal administration of FSjRPI-27 showed protection when dosed 6 h prior to and at infection, and then every 2 days post-infection, with 100 % survival and no toxicity at 104 plaque-forming units per mouse vs. buffer control. At 5-fold higher virus dose, FSjRPI-27 reduced mortality and yielded reduced viral titers in bronchioalveolar fluid and lung homogenates vs. buffer control. These findings suggest the potential application of seaweed-based sulfated polysaccharides as promising anti-SARS-CoV-2 prophylactics.
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