ReviewMolecules (Basel, Switzerland)2022
Covalent Reversible Inhibitors of Cysteine Proteases Containing the Nitrile Warhead: Recent Advancement in the Field of Viral and Parasitic Diseases.
Review in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Discovery of Novel Inhibitors of Cruzain Cysteine Protease ofCurrent medicinal chemistry · 2024Pooled it
- Article
- Nitrile-Based Inhibitors Targeting both SARS-CoV‑2 Main Protease and Human Cathepsin L.ACS medicinal chemistry letters · 2026Article
- Fragment-Based Design of Targeted Covalent Inhibitors: The Scope and Limitation of Linking Approaches.ChemMedChem · 2026Article
- Photoactivation in Chemotherapeutic Compounds for Cancer Treatment: Opportunities Beyond Photodynamic Therapy.Bioinorganic chemistry and applications · 2026Review
- MnM-W-MMGBSA: A Computational Strategy to Improve Relative Binding Free Energies of Protein-Protein Interaction Systems.The journal of physical chemistry. B · 2025Article
- Inhibition of dimeric SARS-CoV-2 Mpro displays positive cooperativity and a mixture of covalent and non-covalent binding.iScience · 2025Article
- Advances in Cysteine Protease B Inhibitors for Leishmaniasis Treatment.Current drug targets · 2025Review
- Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Nonstructural Protein Inhibitors.Journal of the American Chemical Society · 2024Article
- Enantioconvergent Cross-Nucleophile Coupling: Copper-Catalyzed Deborylative Cyanation.Angewandte Chemie (International ed. in English) · 2024Article
- Development and Application of Reversible and Irreversible Covalent Probes for Human and Mouse Cathepsin-K Activity Detection, Revealing Nuclear Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Advances in the Search for SARS-CoV-2 MPathogens (Basel, Switzerland) · 2024Review
- Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts.Advanced healthcare materials · 2024Article
- Review
- Flavin-Mediated Photocatalysis Provides a General Platform for Sulfide C-H Functionalization.ACS catalysis · 2024Article
- Covalent-reversible peptide-based protease inhibitors. Design, synthesis, and clinical success stories.Amino acids · 2023Review
- Exploring diverse reactive warheads for the design of SARS-CoV-2 main protease inhibitors.European journal of medicinal chemistry · 2023Article
- Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors-A Comprehensive Reactivity and Selectivity Study.International journal of molecular sciences · 2023Article
- The pyridazine heterocycle in molecular recognition and drug discovery.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023Review
- Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine.Journal of medicinal chemistry · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
In the field of drug discovery, the nitrile group is well represented among drugs and biologically active compounds. It can form both non-covalent and covalent interactions with diverse biological targets, and it is amenable as an electrophilic warhead for covalent inhibition. The main advantage of the nitrile group as a warhead is mainly due to its milder electrophilic character relative to other more reactive groups (e.g., -CHO), reducing the possibility of unwanted reactions that would hinder the development of safe drugs, coupled to the ease of installation through different synthetic approaches. The covalent inhibition is a well-assessed design approach for serine, threonine, and cysteine protease inhibitors. The mechanism of hydrolysis of these enzymes involves the formation of a covalent acyl intermediate, and this mechanism can be exploited by introducing electrophilic warheads in order to mimic this covalent intermediate. Due to the relevant role played by the cysteine protease in the survival and replication of infective agents, spanning from viruses to protozoan parasites, we will review the most relevant and recent examples of protease inhibitors presenting a nitrile group that have been introduced to form or to facilitate the formation of a covalent bond with the catalytic cysteine active site residue.
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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.