Polysulfates Block SARS-CoV-2 Uptake via Electrostatic Interactions
semanticscholar(2021)
摘要
Here we report that
negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via
electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by
heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched
polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor,
with a half-maximal inhibitory concentration (IC50) of 67 μg/mL (approx. 1.6 μM). This
synthetic polysulfates exhibit more than 60-fold higher virus inhibitory
activity than heparin (IC50: 4084 μg/mL), along
with much lower anticoagulant activity. Furthermore, in molecular dynamics
simulations, we verified that LPGS can bind stronger to the spike protein than
heparin, and that LPGS can interact even more with the spike protein of the new
N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into
host cells can be blocked via electrostatic interaction, therefore LPGS can serve
as a blueprint for the design of novel viral inhibitors of SARS-CoV-2.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要