ArticlePLoS biology2005
Design of wide-spectrum inhibitors targeting coronavirus main proteases.
Article in PLoS biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 415 papers.
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
415 citing papers in PubMed, 772 citations in OpenAlex.
- Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir.Clinical pharmacology and therapeutics · 2022Trial
- Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.The New England journal of medicine · 2022Trial
- Hitting Coronaviruses Where It Hurts: Antiviral Strategies Targeting Viral Proteins.ChemMedChem · 2026Review
- SARS-CoV-2 3CL protease interaction with host factors - identifying novel drug targets.Archives of virology · 2026Review
- 9-fluorenone-based synthetic sulfonamide compounds as dual inhibitors of SARS-CoV-2 Main-Protease and Papain-like Protease.Molecular diversity · 2026Article
- Cooperativity and communication between the active sites of the dimeric SARS-CoV-2 main protease.Science advances · 2026Article
- In Silico Optimization of Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2.Life (Basel, Switzerland) · 2025Article
- PLiSAGE: enhancing protein-ligand interaction prediction with multimodal surface and geometry encoding.Bioinformatics (Oxford, England) · 2025Article
- Thapsigargin suppresses porcine hemagglutinating encephalomyelitis virus replication by disrupting host energy metabolism.Virologica Sinica · 2025Article
- Generative adversarial network (GAN) model-based design of potent SARS-CoV-2 MMolecular diversity · 2025Article
- A Structure-Based Computational Pipeline for Broad-Spectrum Antiviral Discovery.bioRxiv : the preprint server for biology · 2025Article
- An orally available MNature communications · 2025Article
- K36-based inhibitor analogs as potential therapeutics against SARS-CoV-2 main protease (Mpro): a computational investigation.Scientific reports · 2025Article
- The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D.Virologica Sinica · 2025Article
- Development of Peptidomimetic PROTACs as Potential Degraders of 3-Chymotrypsin-like Protease of SARS-CoV-2.International journal of molecular sciences · 2025Article
- A Reflection on the Use of Molecular Simulation to Respond to SARS-CoV-2 Pandemic Threats.The journal of physical chemistry letters · 2025Review
- Dihydropyrimidine-2-thione derivatives as SARS-CoV-2 main protease inhibitors: synthesis, SAR andRSC advances · 2025Article
- Research Progress on the Structure and Function, Immune Escape Mechanism, Antiviral Drug Development Methods, and Clinical Use of SARS-CoV-2 MMolecules (Basel, Switzerland) · 2025Review
- Screening of Natural Compounds as Inhibitor of MCurrent pharmaceutical design · 2025Article
- Exploration of Specific Fluoroquinolone Interaction with SARS-CoV-2 Main Protease (Mpro) to Battle COVID-19: DFT, Molecular Docking, ADME and Cardiotoxicity Studies.Molecules (Basel, Switzerland) · 2024Article
355 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of Mpro-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.
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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.