ArticleJournal of medicinal chemistry2021
Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
29 citing papers in PubMed, 58 citations in OpenAlex.
- 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
- Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Identifying Inhibitor-SARS-CoV2-3CLMolecules (Basel, Switzerland) · 2025Article
- Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Nonstructural Protein Inhibitors.Journal of the American Chemical Society · 2024Article
- Novel Alkynylamide-Based Nonpeptidic Allosteric Inhibitors for SARS-CoV-2 3-Chymotrypsin-like Protease.ACS pharmacology & translational science · 2024Article
- 3-chymotrypsin-like protease in SARS-CoV-2.Bioscience reports · 2024Review
- Potent small molecule inhibitors against the 3C protease of foot-and-mouth disease virus.Microbiology spectrum · 2024Article
- Article
- On the origins of SARS-CoV-2 main protease inhibitors.RSC medicinal chemistry · 2024Review
- Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review.European journal of medicinal chemistry · 2023Review
- Bench-to-bedside: Innovation of small molecule anti-SARS-CoV-2 drugs in China.European journal of medicinal chemistry · 2023Review
- Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives.Biomolecules · 2023Review
- An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition.Nature communications · 2023Article
- Computational Design, Synthesis, and Biophysical Evaluation of β-Amido Boronic Acids as SARS-CoV-2 MMolecules (Basel, Switzerland) · 2023Article
- Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine.Journal of medicinal chemistry · 2023Article
- Advances in research on 3C-like protease (3CLRSC medicinal chemistry · 2023Review
- Broad-Spectrum Cyclopropane-Based Inhibitors of Coronavirus 3C-like Proteases: Biochemical, Structural, and Virological Studies.ACS pharmacology & translational science · 2023Article
- An update on the discovery and development of reversible covalent inhibitors.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023Review
- Roles of host proteases in the entry of SARS-CoV-2.Animal diseases · 2023Review
- Deuterated Drugs and Biomarkers in the COVID-19 Pandemic.ACS omega · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
A series of nondeuterated and deuterated dipeptidyl aldehyde and masked aldehyde inhibitors that incorporate in their structure a conformationally constrained cyclohexane moiety was synthesized and found to potently inhibit severe acute respiratory syndrome coronavirus-2 3CL protease in biochemical and cell-based assays. Several of the inhibitors were also found to be nanomolar inhibitors of Middle East respiratory syndrome coronavirus 3CL protease. The corresponding latent aldehyde bisulfite adducts were found to be equipotent to the precursor aldehydes. High-resolution cocrystal structures confirmed the mechanism of action and illuminated the structural determinants involved in binding. The spatial disposition of the compounds disclosed herein provides an effective means of accessing new chemical space and optimizing pharmacological activity. The cellular permeability of the identified inhibitors and lack of cytotoxicity warrant their advancement as potential therapeutics for COVID-19.
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What OpenQuestion holds
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.