ArticleScience advances2021
Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- TPPS4 inhibits PEDV by stabilizing viral RNA G-quadruplex and promoting ER stress: a transfer-learning-driven discovery.Journal of virology · 2026Article
- RNA-binding landscape of amiloride: large-scale profiling and structural basis of U-U mismatch recognition.RSC chemical biology · 2026Article
- SARS-CoV-2 Antivirals Identified from Small Molecule Modulators of Programmed -1 Ribosomal Frameshifting.ACS infectious diseases · 2026Article
- Decoding the Structural Complexity of Viral RNAs with SHAPE to Guide Antiviral Therapeutics.Viruses · 2026Review
- The RNA promoter for pathogenic orthoflaviviruses replication is universal and serves as target for viral inhibition.PLoS pathogens · 2026Article
- NMR-Based Fragment Screening for RNA-Targeted Drug Discovery.Molecules (Basel, Switzerland) · 2026Review
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
- RNP interfaces as regulatory "active sites": a repurposing strategy for small molecules targeting viral 5'-untranslated regions.Frontiers in molecular biosciences · 2026Article
- Pathogenic Proteins Through the Lens of NMR Spectroscopy: Structural and Functional Insights into Disease.Cell biochemistry and biophysics · 2025Review
- DistRMI: a deep distance-aware neural network for explainable RNA loop motif-small molecule interaction prediction.Briefings in bioinformatics · 2025Article
- Mechanistic studies of small molecule ligands selective to RNA single G bulges.Nucleic acids research · 2025Article
- Crystallographic and cryoEM analyses reveal SARS-CoV-2 SL5 is a mobile T-shaped four-way junction with deep pockets.RNA (New York, N.Y.) · 2025Article
- Article
- Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5' untranslated region.Nature communications · 2025Article
- Targeting RNA with small molecules, from RNA structures to precision medicines: IUPHAR review: 40.British journal of pharmacology · 2024Review
- NMR characterization and ligand binding site of the stem-loop 2 motif from the Delta variant of SARS-CoV-2.RNA (New York, N.Y.) · 2024Article
- Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system.RSC medicinal chemistry · 2024Article
- Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Enterovirus evolution reveals the mechanism of an RNA-targeted antiviral and determinants of viral replication.Science advances · 2024Article
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Authors and funding
16 authors.
Funding
Abstract
The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, emphasized the urgent need for development of novel antivirals. Small-molecule chemical probes offer both to reveal aspects of virus replication and to serve as leads for antiviral therapeutic development. Here, we report on the identification of amiloride-based small molecules that potently inhibit OC43 and SARS-CoV-2 replication through targeting of conserved structured elements within the viral 5′-end. Nuclear magnetic resonance–based structural studies revealed specific amiloride interactions with stem loops containing bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Amilorides represent the first antiviral small molecules that target RNA structures within the 5′ untranslated regions and proximal region of the CoV genomes. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA–targeted antivirals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.