ArticleProceedings of the National Academy of Sciences of the United States of America2022
Thiol-based chemical probes exhibit antiviral activity against SARS-CoV-2 via allosteric disulfide disruption in the spike glycoprotein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Integrating Functional Response and Target Binding for Mechanism-Centered Drug Screening by High-Mass MALDI-MS.ACS central science · 2026Article
- Designing a novel vaccine against COVID-19 based on spike SARS-Cov-2 notable mutations using immunoinformatics approaches.PloS one · 2026Article
- Hydrogen sulfide (H2S) coordinates redox balance, carbon metabolism, and mitochondrial bioenergetics to suppress SARS-CoV-2 infection.PLoS pathogens · 2025Article
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Dynamic Thiol-Disulfide Homeostasis Post-COVID-19 Depends on Age, Gender, and Symptom Severity.Cureus · 2024Article
- Enhanced Surface Accessibility of SARS-CoV-2 Omicron Spike Protein Due to an Altered Glycosylation Profile.ACS infectious diseases · 2024Article
- Exploring Binding Pockets in the Conformational States of the SARS-CoV-2 Spike Trimers for the Screening of Allosteric Inhibitors Using Molecular Simulations and Ensemble-Based Ligand Docking.International journal of molecular sciences · 2024Article
- Functionalizing tandem mass tags for streamlining click-based quantitative chemoproteomics.Communications chemistry · 2024Article
- Selenium-More than Just a Fortuitous Sulfur Substitute in Redox Biology.Molecules (Basel, Switzerland) · 2023Review
- Decoy peptides effectively inhibit the binding of SARS-CoV-2 to ACE2 on oral epithelial cells.Heliyon · 2023Article
- Solid-Phase Compatible Silane-Based Cleavable Linker Enables Custom Isobaric Quantitative Chemoproteomics.Journal of the American Chemical Society · 2023Article
- Soluble SARS-CoV-2 RBD and human ACE2 peptidase domain produced in Drosophila S2 cells show functions evoking virus-cell interface.Protein science : a publication of the Protein Society · 2023Article
- Supersulphides provide airway protection in viral and chronic lung diseases.Nature communications · 2023Article
- SARS-CoV-2 spike proteins react with Au and Si, are electrically conductive and denature at 3 × 10Chemical science · 2023Article
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
- N-acetylcysteine Reduces Inflammasome Activation Induced by SARS-CoV-2 Proteins In Vitro.International journal of molecular sciences · 2022Article
- Article
- Redox stress in COVID-19: Implications for hematologic disorders.Best practice & research. Clinical haematology · 2022Review
- Exploring antiviral and anti-inflammatory effects of thiol drugs in COVID-19.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review.Antioxidants (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The development of small-molecules targeting different components of SARS-CoV-2 is a key strategy to complement antibody-based treatments and vaccination campaigns in managing the COVID-19 pandemic. Here, we show that two thiol-based chemical probes that act as reducing agents, P2119 and P2165, inhibit infection by human coronaviruses, including SARS-CoV-2, and decrease the binding of spike glycoprotein to its receptor, the angiotensin-converting enzyme 2 (ACE2). Proteomics and reactive cysteine profiling link the antiviral activity to the reduction of key disulfides, specifically by disruption of the Cys379-Cys432 and Cys391-Cys525 pairs distal to the receptor binding motif in the receptor binding domain (RBD) of the spike glycoprotein. Computational analyses provide insight into conformation changes that occur when these disulfides break or form, consistent with an allosteric role, and indicate that P2119/P2165 target a conserved hydrophobic binding pocket in the RBD with the benzyl thiol-reducing moiety pointed directly toward Cys432. These collective findings establish the vulnerability of human coronaviruses to thiol-based chemical probes and lay the groundwork for developing compounds of this class, as a strategy to inhibit the SARS-CoV-2 infection by shifting the spike glycoprotein redox scaffold.
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Registered trials
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