ArticleJournal of molecular biology2011
Comparison of SARS and NL63 papain-like protease binding sites and binding site dynamics: inhibitor design implications.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed.
- Divergent resistance pathways amongst SARS-CoV-2 PLpro inhibitors highlight the need for scaffold diversity.PLoS pathogens · 2025Article
- Potential Broad-Spectrum Antiviral Agents: A Key Arsenal Against Newly Emerging and Reemerging Respiratory RNA Viruses.International journal of molecular sciences · 2025Review
- Mutational profiling of SARS-CoV-2 papain-like protease reveals requirements for function, structure, and drug escape.Nature communications · 2024Article
- Molecular mechanisms of human coronavirus NL63 infection and replication.Virus research · 2023Review
- Computational study of the binding orientation and affinity of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-1 considering the protein flexibility by using molecular dynamics and cross-docking.Frontiers in molecular biosciences · 2023Article
- Pathfinder-Driven Chemical Space Exploration and Multiparameter Optimization in Tandem with Glide/IFD and QSAR-Based Active Learning Approach to Prioritize Design Ideas for FEP+ Calculations of SARS-CoV-2 PLMolecules (Basel, Switzerland) · 2022Article
- Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19.Briefings in bioinformatics · 2021Article
- Accelerating the repurposing of FDA-approved drugs against coronavirus disease-19 (COVID-19).RSC advances · 2020Article
- Tackling SARS-CoV-2: proposed targets and repurposed drugs.Future medicinal chemistry · 2020Review
- Structural and biochemical characterization of SADS-CoV papain-like protease 2.Protein science : a publication of the Protein Society · 2020Article
- Insights Into Dynamics of Inhibitor and Ubiquitin-Like Protein Binding in SARS-CoV-2 Papain-Like Protease.Frontiers in molecular biosciences · 2020Article
- Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine.Antiviral research · 2018Article
- Validating Molecular Dynamics Simulations against Experimental Observables in Light of Underlying Conformational Ensembles.The journal of physical chemistry. B · 2018Article
- Structure and Function of Viral Deubiquitinating Enzymes.Journal of molecular biology · 2017Review
- Coronaviruses - drug discovery and therapeutic options.Nature reviews. Drug discovery · 2016Review
- Recent Advances in the Discovery of Deubiquitinating Enzyme Inhibitors.Progress in medicinal chemistry · 2016Review
- Structural view and substrate specificity of papain-like protease from avian infectious bronchitis virus.The Journal of biological chemistry · 2015Article
- p53 degradation by a coronavirus papain-like protease suppresses type I interferon signaling.The Journal of biological chemistry · 2015Article
- Catalytic function and substrate specificity of the papain-like protease domain of nsp3 from the Middle East respiratory syndrome coronavirus.Journal of virology · 2014Article
- Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir.Virus research · 2014Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The human severe acute respiratory syndrome coronavirus (SARS-CoV) and the NL63 coronaviruses are human respiratory pathogens for which no effective antiviral treatment exists. The papain-like cysteine proteases encoded by the coronavirus (SARS-CoV: PLpro; NL63: PLP1 and PLP2) represent potential targets for antiviral drug development. Three recent inhibitor-bound PLpro structures highlight the role of an extremely flexible six-residue loop in inhibitor binding. The high binding site plasticity is a major challenge in computational drug discovery/design efforts. From conventional molecular dynamics and accelerated molecular dynamics (aMD) simulations, we find that with conventional molecular dynamics simulation, PLpro translationally samples the open and closed conformation of BL2 loop on a picosecond-nanosecond timescale but does not reproduce the peptide bond inversion between loop residues Tyr269 and Gln270 that is observed on inhibitor GRL0617 binding. Only aMD simulation, starting from the closed loop conformation, reproduced the 180° ϕ-ψ dihedral rotation back to the open loop state. The Tyr-Gln peptide bond inversion appears to involve a progressive conformational change of the full loop, starting at one side, and progressing to the other. We used the SARS-CoV apo X-ray structure to develop a model of the NL63-PLP2 catalytic site. Superimposition of the PLP2 model on the PLpro X-ray structure identifies binding site residues in PLP2 that contribute to the distinct substrate cleavage site specificities between the two proteases. The topological and electrostatic differences between the two protease binding sites also help explain the selectivity of non-covalent PLpro inhibitors.
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Registered trials
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