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

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

  • Sci Adv. 2024 Apr 12;10(15):eadl4393. doi: 10.1126/sciadv.adl4393.
Yuanqin Min 1,  Wei Xiong 2,  Wei Shen 2,  Xingyu Liu 2,  Qianqian Qi 2,  Yuanyuan Zhang 2,  Ruochen Fan 2,  Fang Fu 2,  Heng Xue 1,  Hang Yang 1,  Xiulian Sun 1,  Yunjia Ning 1,  Tian Tian 2,  Xiang Zhou 2
Affiliations

Affiliations

  • 1 Wuhan Institute of Virology; Hubei Jiangxia Laboratory; Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430200, Hubei, China.
  • 2 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.
PMID: 38598625 DOI: 10.1126/sciadv.adl4393
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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