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Sci Adv . Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera

tetano

Editor, Senior Moderator
Sci Adv


. 2024 Apr 12;10(15):eadl4393.
doi: 10.1126/sciadv.adl4393. Epub 2024 Apr 10. Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera

Yuanqin Min[SUP] 1 [/SUP], Wei Xiong[SUP] 2 [/SUP], Wei Shen[SUP] 2 [/SUP], Xingyu Liu[SUP] 2 [/SUP], Qianqian Qi[SUP] 2 [/SUP], Yuanyuan Zhang[SUP] 2 [/SUP], Ruochen Fan[SUP] 2 [/SUP], Fang Fu[SUP] 2 [/SUP], Heng Xue[SUP] 1 [/SUP], Hang Yang[SUP] 1 [/SUP], Xiulian Sun[SUP] 1 [/SUP], Yunjia Ning[SUP] 1 [/SUP], Tian Tian[SUP] 2 [/SUP], Xiang Zhou[SUP] 2 [/SUP]



Affiliations
Abstract

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 asset in the development of innovative antiviral drugs.


 
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