1'-cyanocytidine-5'-isobutyryl for COVID-19

 1'-cyanocytidine-5'-isobutyryl has been reported as potentially beneficial for COVID-19 in the following study.
COVID-19 involves the interplay of 350+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 10,000+ potential treatments. c19early.org analyzes 200+ treatments. We have not reviewed 1'-cyanocytidine-5'-isobutyryl in detail.
Amblard et al., 1′-Cyanocytidine-5′-isobutyryl is a potent SARS-CoV-2 inhibitor in culture and infected Syrian hamsters, Science Advances, doi:10.1126/sciadv.adz5913
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 epidemic is relatively under control due to the rapid development and deployment of vaccines and a few drugs. However, challenges persist, as new variants and issues with vaccine durability may compromise their effectiveness. Here, we report the discovery and evaluation of 1′-cyanocytidine (CNC), a nontoxic, next-generation nucleoside analog that displays submicromolar inhibition of SARS-CoV-2 replication in various cell and 3D HAE-ALI primary culture systems. Intracellularly, CNC is metabolized to its active 5′-triphosphate form (CNC-TP), targeting the viral RNA–dependent RNA polymerase. Pre–steady-state kinetic analysis revealed CNC-TP is a reversible, competitive inhibitor. The 5′-isobutyryl ester prodrug of CNC (CN iBu C), which rapidly converts to CNC in mouse and hamster plasma, substantially reduced viral RNA levels and lung infectious virus titers in a Syrian hamster model after intraperitoneal and oral dosing. With favorable pharmacokinetics, bioavailability, and safety profiles, CNC and CN iBu C represent promising candidates for SARS-CoV-2 therapy.