ArticleNature communications2022
Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Efficacy and safety of 3CL protease inhibitors in patients with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials.Virology journal · 2025Pooled it
- Integrated Computational Study Prioritizes Drug-like Para-Flavonoids as Candidate SARS-CoV-2 MCurrent issues in molecular biology · 2026Article
- Multi-antigen coronavirus vaccine induces potent and durable cross-protection against multiple SARS-CoV-2 variants.NPJ vaccines · 2026Article
- Recent Advances in the Design of Inhibitors Targeting the Viral Entry and Replication of the SARS-CoV-2 Virus, Driven by In Silico Approaches.Molecules (Basel, Switzerland) · 2026Review
- Machine learning-based prediction of SARS-CoV-2 bioactivity: integrating ICBMC bioinformatics · 2026Article
- A Novel Covalent Inhibitor Fragment for the SARS-CoV-2 Main Protease Identified by Target-Specific Deep Learning.ACS chemical biology · 2026Article
- Review on advances in small molecule inhibitors on the treatment of inflammatory bowel disease.Molecular biology reports · 2026Review
- In Silico Optimization of Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2.Life (Basel, Switzerland) · 2025Article
- Room-Temperature Nucleophilic Aromatic Substitution of 2‑Halopyridinium Ketene Hemiaminals with Sulfur Nucleophiles.ACS omega · 2025Article
- Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Prospects for the structure‒function evolution of SARS-CoV-2 main protease inhibitors.Journal of computer-aided molecular design · 2025Review
- Eco-friendly synthesis of Ag/CeORSC advances · 2025Article
- Identifying Inhibitor-SARS-CoV2-3CLMolecules (Basel, Switzerland) · 2025Article
- Potential Broad-Spectrum Antiviral Agents: A Key Arsenal Against Newly Emerging and Reemerging Respiratory RNA Viruses.International journal of molecular sciences · 2025Review
- A multiplex method for rapidly identifying viral protease inhibitors.Molecular systems biology · 2025Article
- Development of small molecule non-covalent coronavirus 3CL protease inhibitors from DNA-encoded chemical library screening.Nature communications · 2025Article
- Dynamics of spike-specific neutralizing antibodies across five-year emerging SARS-CoV-2 variants of concern reveal conserved epitopes that protect against severe COVID-19.Frontiers in immunology · 2025Article
- Human E3 ubiquitin ligases: accelerators and brakes for SARS-CoV-2 infection.Biochemical Society transactions · 2024Review
- Dynamics of Spike-Specific Neutralizing Antibodies Across Five-Year Emerging SARS-CoV-2 Variants of Concern Reveal Conserved Epitopes that Protect Against Severe COVID-19.bioRxiv : the preprint server for biology · 2024Article
- Review
Corrections and comments
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Authors and funding
32 authors at 6 institutions in 2 countries.
Funding
Abstract
The SARS-CoV-2 3CL protease is a critical drug target for small molecule COVID-19 therapy, given its likely druggability and essentiality in the viral maturation and replication cycle. Based on the conservation of 3CL protease substrate binding pockets across coronaviruses and using screening, we identified four structurally distinct lead compounds that inhibit SARS-CoV-2 3CL protease. After evaluation of their binding specificity, cellular antiviral potency, metabolic stability, and water solubility, we prioritized the GC376 scaffold as being optimal for optimization. We identified multiple drug-like compounds with <10 nM potency for inhibiting SARS-CoV-2 3CL and the ability to block SARS-CoV-2 replication in human cells, obtained co-crystal structures of the 3CL protease in complex with these compounds, and determined that they have pan-coronavirus activity. We selected one compound, termed coronastat, as an optimized lead and characterized it in pharmacokinetic and safety studies in vivo. Coronastat represents a new candidate for a small molecule protease inhibitor for the treatment of SARS-CoV-2 infection for eliminating pandemics involving coronaviruses.
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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.