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.
Sci Adv. 2024 Apr 12;10(15):eadl4393. doi: 10.1126/sciadv.adl4393. Epub 2024 Apr 10.
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.
为了满足对强效严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）治疗药物的迫切需求，本研究引入了一种创新的核苷修饰策略，利用核糖核酸酶靶向嵌合体。通过将核糖核酸酶 L 招募物无缝整合到核苷中，我们解决了 RNA 识别挑战，并有效地抑制了人细胞中的严重急性呼吸综合征冠状病毒 2 复制。值得注意的是，在核糖 2'-位修饰的核苷优于在碱基修饰的核苷。我们使用仓鼠模型进行的体内验证进一步增强了这种核苷修饰方法的前景，使其成为开发创新型抗病毒药物的有价值的资产。
