2'-RIBOTAC-U is a ribonuclease (RNase) targeting chimeras ( RIBOTACs ) and SARS-CoV-2 replication inhibitor. 2'-RIBOTAC-U is composed of a metabolic handle (Blue), a linker (Black) and a RNase L recruiter (Pink). RIBOTACs recruits cellular RNases to specific RNA targets, thereby leading to the degradation of these RNAs.