Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera
Yuan‐Qin Min, Wei Xiong, Wei Shen, Xingyu Liu, Qianqian Qi, Yuanyuan Zhang, Ruochen Fan, Fang Fu, Heng Xue, Hang Yang, Xiulian Sun, Yun‐Jia Ning, Tian Tian, Xiang Zhou
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.