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Antiviral drug design based on structural insights into the N-terminal domain and C-terminal domain of the SARS-CoV-2 nucleocapsid protein

作者:栾晓东,张抒扬等
发表年份:2022年
发表期刊:Science Bulletin
作者单位:清华大学,协和医学院等
地区:北京市


文章摘要

Nucleocapsid (N) protein plays crucial roles in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including the formation of ribonucleoprotein (RNP) complex with the viral RNA. Here we reported the crystal structures of the N-terminal domain (NTD) and C-terminal domain (CTD) of the N protein and an NTD-RNA complex. Our structures reveal a unique tetramer organization of NTD and identify a distinct RNA binding mode in the NTD-RNA complex, which could contribute to the formation of the RNP complex. We also screened small molecule inhibitors of N-NTD and N-CTD and discovered that ceftriaxone sodium, an antibiotic, can block the binding of RNA to NTD and inhibit the formation of the RNP complex. These results together could facilitate the further research of antiviral drug design targeting N protein.

实验方法

使用机型:Biacore S200
实验类型:亲和力/动力学表征,竞争性结合
样品类型:配体:SARS-CoV-2 N-NTD蛋白;分析物:ceftriaxone sodium,RNA
实验芯片:S系列CM5芯片 
配体固定方式:氨基偶联
运行缓冲液:PBS

产品信息

类别 货号 产品名称 规格
主机 Biacore S200
芯片 29104988 S系列CM5芯片 1片
芯片 BR100530 S系列CM5芯片 3片
芯片 29149603 S系列CM5芯片 10片
试剂盒 BR100050 氨基偶联试剂盒 
运行缓冲液 BR100672 PBS (10×)  1 × 1000 mL 

Reference

Luan X, Li X, Li Y, Su G, Yin W, Jiang Y, Xu N, Wang F, Cheng W, Jin Y, Zhang L, Xu HE, Xue Y, Zhang S. Antiviral drug design based on structural insights into the N-terminal domain and C-terminal domain of the SARS-CoV-2 nucleocapsid protein. Sci Bull (Beijing). 2022 Nov 30;67(22):2327-2335. doi: 10.1016/j.scib.2022.10.021. Epub 2022 Oct 27. PMID: 36317101; PMCID: PMC9605790.