Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.
作者：
Min, Yuanqin;Xiong, Wei;Shen, Wei;Liu, Xingyu;Qi, Qianqian;...
通讯作者：
Tian Tian
作者机构：
Wuhan Institute of Virology
Hubei Jiangxia Laboratory
Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430200, Hubei, China
Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan 430072, Hubei, China
通讯机构：
Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan 430072, Hubei, China.
语种：
英文
期刊：
Science Advances
ISSN：
2375-2548
年：
2024
卷：
10
期：
15
页码：
eadl4393
基金类别：
National Natural Science Foundation of China: 22177089;National Natural Science Foundation of China: 21721005;National Natural Science Foundation of China: 92153303;National Natural Science Foundation of China: 22037004;National Natural Science Foundation of China: 22177088;Fundamental Research Funds for the Central Universities: 2042023kf0204
摘要：
In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating ribonuclease L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit severe acute respiratory syndrome coronavirus 2 replication in human cells. Notably, nucleosides tailored at the ribose 2'-position outperform those modified at the nucleobase. Our in vivo validation using hamster models further bolsters the promise of this nucleoside tailoring approach, positioning it as a valuable ass...
