%0 Journal Article
%T Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.
%A Min Y
%A Xiong W
%A Shen W
%A Liu X
%A Qi Q
%A Zhang Y
%A Fan R
%A Fu F
%A Xue H
%A Yang H
%A Sun X
%A Ning Y
%A Tian T
%A Zhou X
%J Sci Adv
%V 10
%N 15
%D 2024 Apr 12
%M 38598625
%F 14.957
%R 10.1126/sciadv.adl4393
%X 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.