2-Thiouridine is an orally active modified nucleobase. 2-Thiouridine stabilizes U:A base pairs and destabilizes U:G wobble base pairs. 2-Thiouridine significantly improves the efficiency and accuracy of nonenzymatic replication of mixed-sequence A/U-containing RNA templates. 2-Thiouridine exhibits antiviral activity against multiple positive-sense single-stranded RNA viruses (DENV2, ZIKV, YFV, JEV, WNV, CHIKV, human coronaviruses ( [HCoV]-229E, HCoV-OC43, SARS-CoV), and MERS-CoV)[1][2][3][4].