ArticleScience advances2025
1'-Cyanocytidine-5'-isobutyryl is a potent SARS-CoV-2 inhibitor in culture and infected Syrian hamsters.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Towards broader-spectrum direct-acting antivirals against RNA viruses.Nature reviews. Microbiology · 2026Review
- The 5'-Isobutyryl Ester Prodrug of 4'-Thiouridine Inhibits SARS-CoV‑2 Replication in Culture and in a Syrian Hamster Infection Model.ACS omega · 2026Article
- Stereoselective synthesis of 1'-α-cyano carbocyclic pyrimidine nucleoside analogsOrganic & biomolecular chemistry · 2026Article
- Slow PPThe Journal of biological chemistry · 2026Article
- Extending the Targets for Coronavirus Antivirals Beyond That of Approved Drugs: Insights From Preclinical Research.Microbial biotechnology · 2026Review
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Authors and funding
20 authors.
Funding
Abstract
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
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